Critical role of glutamine metabolism in cardiomyocytes under oxidative stress
Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells dep...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Watanabe, Koichi [verfasserIn] Nagao, Manabu [verfasserIn] Toh, Ryuji [verfasserIn] Irino, Yasuhiro [verfasserIn] Shinohara, Masakazu [verfasserIn] Iino, Takuya [verfasserIn] Yoshikawa, Sachiko [verfasserIn] Tanaka, Hidekazu [verfasserIn] Satomi-Kobayashi, Seimi [verfasserIn] Ishida, Tatsuro [verfasserIn] Hirata, Ken-ichi [verfasserIn] |
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| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Biochemical and biophysical research communications - Orlando, Fla. : Academic Press, 1959, 534, Seite 687-693 |
|---|---|
| Übergeordnetes Werk: |
volume:534 ; pages:687-693 |
| DOI / URN: |
10.1016/j.bbrc.2020.11.018 |
|---|
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ELV005298520 |
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| 520 | |a Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. | ||
| 650 | 4 | |a Glutaminolysis | |
| 650 | 4 | |a α-ketoglutarate | |
| 650 | 4 | |a Glutaminase | |
| 650 | 4 | |a Metabolic remodeling | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Glutathione | |
| 700 | 1 | |a Nagao, Manabu |e verfasserin |4 aut | |
| 700 | 1 | |a Toh, Ryuji |e verfasserin |4 aut | |
| 700 | 1 | |a Irino, Yasuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Shinohara, Masakazu |e verfasserin |4 aut | |
| 700 | 1 | |a Iino, Takuya |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshikawa, Sachiko |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Hidekazu |e verfasserin |4 aut | |
| 700 | 1 | |a Satomi-Kobayashi, Seimi |e verfasserin |4 aut | |
| 700 | 1 | |a Ishida, Tatsuro |e verfasserin |0 (orcid)0000-0002-1724-0057 |4 aut | |
| 700 | 1 | |a Hirata, Ken-ichi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochemical and biophysical research communications |d Orlando, Fla. : Academic Press, 1959 |g 534, Seite 687-693 |h Online-Ressource |w (DE-627)254231691 |w (DE-600)1461396-7 |w (DE-576)103373039 |x 0006-291X |7 nnns |
| 773 | 1 | 8 | |g volume:534 |g pages:687-693 |
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| 936 | b | k | |a 35.70 |j Biochemie: Allgemeines |
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2020 |
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10.1016/j.bbrc.2020.11.018 doi (DE-627)ELV005298520 (ELSEVIER)S0006-291X(20)32062-3 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 35.70 bkl 42.12 bkl Watanabe, Koichi verfasserin (orcid)0000-0002-7253-0655 aut Critical role of glutamine metabolism in cardiomyocytes under oxidative stress 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. Glutaminolysis α-ketoglutarate Glutaminase Metabolic remodeling Oxidative stress Glutathione Nagao, Manabu verfasserin aut Toh, Ryuji verfasserin aut Irino, Yasuhiro verfasserin aut Shinohara, Masakazu verfasserin aut Iino, Takuya verfasserin aut Yoshikawa, Sachiko verfasserin aut Tanaka, Hidekazu verfasserin aut Satomi-Kobayashi, Seimi verfasserin aut Ishida, Tatsuro verfasserin (orcid)0000-0002-1724-0057 aut Hirata, Ken-ichi verfasserin aut Enthalten in Biochemical and biophysical research communications Orlando, Fla. : Academic Press, 1959 534, Seite 687-693 Online-Ressource (DE-627)254231691 (DE-600)1461396-7 (DE-576)103373039 0006-291X nnns volume:534 pages:687-693 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.70 Biochemie: Allgemeines 42.12 Biophysik AR 534 687-693 |
| spelling |
10.1016/j.bbrc.2020.11.018 doi (DE-627)ELV005298520 (ELSEVIER)S0006-291X(20)32062-3 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 35.70 bkl 42.12 bkl Watanabe, Koichi verfasserin (orcid)0000-0002-7253-0655 aut Critical role of glutamine metabolism in cardiomyocytes under oxidative stress 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. Glutaminolysis α-ketoglutarate Glutaminase Metabolic remodeling Oxidative stress Glutathione Nagao, Manabu verfasserin aut Toh, Ryuji verfasserin aut Irino, Yasuhiro verfasserin aut Shinohara, Masakazu verfasserin aut Iino, Takuya verfasserin aut Yoshikawa, Sachiko verfasserin aut Tanaka, Hidekazu verfasserin aut Satomi-Kobayashi, Seimi verfasserin aut Ishida, Tatsuro verfasserin (orcid)0000-0002-1724-0057 aut Hirata, Ken-ichi verfasserin aut Enthalten in Biochemical and biophysical research communications Orlando, Fla. : Academic Press, 1959 534, Seite 687-693 Online-Ressource (DE-627)254231691 (DE-600)1461396-7 (DE-576)103373039 0006-291X nnns volume:534 pages:687-693 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.70 Biochemie: Allgemeines 42.12 Biophysik AR 534 687-693 |
| allfields_unstemmed |
10.1016/j.bbrc.2020.11.018 doi (DE-627)ELV005298520 (ELSEVIER)S0006-291X(20)32062-3 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 35.70 bkl 42.12 bkl Watanabe, Koichi verfasserin (orcid)0000-0002-7253-0655 aut Critical role of glutamine metabolism in cardiomyocytes under oxidative stress 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. Glutaminolysis α-ketoglutarate Glutaminase Metabolic remodeling Oxidative stress Glutathione Nagao, Manabu verfasserin aut Toh, Ryuji verfasserin aut Irino, Yasuhiro verfasserin aut Shinohara, Masakazu verfasserin aut Iino, Takuya verfasserin aut Yoshikawa, Sachiko verfasserin aut Tanaka, Hidekazu verfasserin aut Satomi-Kobayashi, Seimi verfasserin aut Ishida, Tatsuro verfasserin (orcid)0000-0002-1724-0057 aut Hirata, Ken-ichi verfasserin aut Enthalten in Biochemical and biophysical research communications Orlando, Fla. : Academic Press, 1959 534, Seite 687-693 Online-Ressource (DE-627)254231691 (DE-600)1461396-7 (DE-576)103373039 0006-291X nnns volume:534 pages:687-693 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.70 Biochemie: Allgemeines 42.12 Biophysik AR 534 687-693 |
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10.1016/j.bbrc.2020.11.018 doi (DE-627)ELV005298520 (ELSEVIER)S0006-291X(20)32062-3 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 35.70 bkl 42.12 bkl Watanabe, Koichi verfasserin (orcid)0000-0002-7253-0655 aut Critical role of glutamine metabolism in cardiomyocytes under oxidative stress 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. Glutaminolysis α-ketoglutarate Glutaminase Metabolic remodeling Oxidative stress Glutathione Nagao, Manabu verfasserin aut Toh, Ryuji verfasserin aut Irino, Yasuhiro verfasserin aut Shinohara, Masakazu verfasserin aut Iino, Takuya verfasserin aut Yoshikawa, Sachiko verfasserin aut Tanaka, Hidekazu verfasserin aut Satomi-Kobayashi, Seimi verfasserin aut Ishida, Tatsuro verfasserin (orcid)0000-0002-1724-0057 aut Hirata, Ken-ichi verfasserin aut Enthalten in Biochemical and biophysical research communications Orlando, Fla. : Academic Press, 1959 534, Seite 687-693 Online-Ressource (DE-627)254231691 (DE-600)1461396-7 (DE-576)103373039 0006-291X nnns volume:534 pages:687-693 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.70 Biochemie: Allgemeines 42.12 Biophysik AR 534 687-693 |
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10.1016/j.bbrc.2020.11.018 doi (DE-627)ELV005298520 (ELSEVIER)S0006-291X(20)32062-3 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 35.70 bkl 42.12 bkl Watanabe, Koichi verfasserin (orcid)0000-0002-7253-0655 aut Critical role of glutamine metabolism in cardiomyocytes under oxidative stress 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. Glutaminolysis α-ketoglutarate Glutaminase Metabolic remodeling Oxidative stress Glutathione Nagao, Manabu verfasserin aut Toh, Ryuji verfasserin aut Irino, Yasuhiro verfasserin aut Shinohara, Masakazu verfasserin aut Iino, Takuya verfasserin aut Yoshikawa, Sachiko verfasserin aut Tanaka, Hidekazu verfasserin aut Satomi-Kobayashi, Seimi verfasserin aut Ishida, Tatsuro verfasserin (orcid)0000-0002-1724-0057 aut Hirata, Ken-ichi verfasserin aut Enthalten in Biochemical and biophysical research communications Orlando, Fla. : Academic Press, 1959 534, Seite 687-693 Online-Ressource (DE-627)254231691 (DE-600)1461396-7 (DE-576)103373039 0006-291X nnns volume:534 pages:687-693 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 35.70 Biochemie: Allgemeines 42.12 Biophysik AR 534 687-693 |
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Enthalten in Biochemical and biophysical research communications 534, Seite 687-693 volume:534 pages:687-693 |
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Enthalten in Biochemical and biophysical research communications 534, Seite 687-693 volume:534 pages:687-693 |
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Glutaminolysis α-ketoglutarate Glutaminase Metabolic remodeling Oxidative stress Glutathione |
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Biochemical and biophysical research communications |
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Watanabe, Koichi @@aut@@ Nagao, Manabu @@aut@@ Toh, Ryuji @@aut@@ Irino, Yasuhiro @@aut@@ Shinohara, Masakazu @@aut@@ Iino, Takuya @@aut@@ Yoshikawa, Sachiko @@aut@@ Tanaka, Hidekazu @@aut@@ Satomi-Kobayashi, Seimi @@aut@@ Ishida, Tatsuro @@aut@@ Hirata, Ken-ichi @@aut@@ |
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2020-01-01T00:00:00Z |
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Watanabe, Koichi |
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Watanabe, Koichi ddc 570 fid BIODIV bkl 35.70 bkl 42.12 misc Glutaminolysis misc α-ketoglutarate misc Glutaminase misc Metabolic remodeling misc Oxidative stress misc Glutathione Critical role of glutamine metabolism in cardiomyocytes under oxidative stress |
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570 DE-600 BIODIV DE-30 fid 35.70 bkl 42.12 bkl Critical role of glutamine metabolism in cardiomyocytes under oxidative stress Glutaminolysis α-ketoglutarate Glutaminase Metabolic remodeling Oxidative stress Glutathione |
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Critical role of glutamine metabolism in cardiomyocytes under oxidative stress |
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Watanabe, Koichi Nagao, Manabu Toh, Ryuji Irino, Yasuhiro Shinohara, Masakazu Iino, Takuya Yoshikawa, Sachiko Tanaka, Hidekazu Satomi-Kobayashi, Seimi Ishida, Tatsuro Hirata, Ken-ichi |
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critical role of glutamine metabolism in cardiomyocytes under oxidative stress |
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Critical role of glutamine metabolism in cardiomyocytes under oxidative stress |
| abstract |
Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. |
| abstractGer |
Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. |
| abstract_unstemmed |
Background: Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear.Objective: To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium.Methods and results: The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H2O2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H2O2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. |
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These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H2O2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels.Conclusion: Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. 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