Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux
Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, w...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Rodrigues, Silvia D. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020transfer abstract |
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| Schlagwörter: |
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| Umfang: |
7 |
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| Übergeordnetes Werk: |
Enthalten in: Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag - Zhang, Zhikun ELSEVIER, 2019, BBRC, Orlando, Fla |
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| Übergeordnetes Werk: |
volume:523 ; year:2020 ; number:1 ; day:26 ; month:02 ; pages:123-129 ; extent:7 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.bbrc.2019.12.022 |
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| 245 | 1 | 0 | |a Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux |
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| 520 | |a Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. | ||
| 520 | |a Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. | ||
| 650 | 7 | |a Oxidative stress |2 Elsevier | |
| 650 | 7 | |a Uremic toxins |2 Elsevier | |
| 650 | 7 | |a Protein carbonylation |2 Elsevier | |
| 650 | 7 | |a Autophagy impairment |2 Elsevier | |
| 650 | 7 | |a Chronic kidney disease |2 Elsevier | |
| 700 | 1 | |a Santos, Sabrina S. |4 oth | |
| 700 | 1 | |a Meireles, Tassiana |4 oth | |
| 700 | 1 | |a Romero, Natalia |4 oth | |
| 700 | 1 | |a Glorieux, Griet |4 oth | |
| 700 | 1 | |a Pecoits-Filho, Roberto |4 oth | |
| 700 | 1 | |a Zhang, Donna D. |4 oth | |
| 700 | 1 | |a Nakao, Lia S. |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Academic Press |a Zhang, Zhikun ELSEVIER |t Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag |d 2019 |d BBRC |g Orlando, Fla |w (DE-627)ELV002811154 |
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10.1016/j.bbrc.2019.12.022 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000895.pica (DE-627)ELV04924793X (ELSEVIER)S0006-291X(19)32342-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Rodrigues, Silvia D. verfasserin aut Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux 2020transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Oxidative stress Elsevier Uremic toxins Elsevier Protein carbonylation Elsevier Autophagy impairment Elsevier Chronic kidney disease Elsevier Santos, Sabrina S. oth Meireles, Tassiana oth Romero, Natalia oth Glorieux, Griet oth Pecoits-Filho, Roberto oth Zhang, Donna D. oth Nakao, Lia S. oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:523 year:2020 number:1 day:26 month:02 pages:123-129 extent:7 https://doi.org/10.1016/j.bbrc.2019.12.022 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 523 2020 1 26 0226 123-129 7 |
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10.1016/j.bbrc.2019.12.022 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000895.pica (DE-627)ELV04924793X (ELSEVIER)S0006-291X(19)32342-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Rodrigues, Silvia D. verfasserin aut Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux 2020transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Oxidative stress Elsevier Uremic toxins Elsevier Protein carbonylation Elsevier Autophagy impairment Elsevier Chronic kidney disease Elsevier Santos, Sabrina S. oth Meireles, Tassiana oth Romero, Natalia oth Glorieux, Griet oth Pecoits-Filho, Roberto oth Zhang, Donna D. oth Nakao, Lia S. oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:523 year:2020 number:1 day:26 month:02 pages:123-129 extent:7 https://doi.org/10.1016/j.bbrc.2019.12.022 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 523 2020 1 26 0226 123-129 7 |
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10.1016/j.bbrc.2019.12.022 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000895.pica (DE-627)ELV04924793X (ELSEVIER)S0006-291X(19)32342-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Rodrigues, Silvia D. verfasserin aut Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux 2020transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Oxidative stress Elsevier Uremic toxins Elsevier Protein carbonylation Elsevier Autophagy impairment Elsevier Chronic kidney disease Elsevier Santos, Sabrina S. oth Meireles, Tassiana oth Romero, Natalia oth Glorieux, Griet oth Pecoits-Filho, Roberto oth Zhang, Donna D. oth Nakao, Lia S. oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:523 year:2020 number:1 day:26 month:02 pages:123-129 extent:7 https://doi.org/10.1016/j.bbrc.2019.12.022 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 523 2020 1 26 0226 123-129 7 |
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10.1016/j.bbrc.2019.12.022 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000895.pica (DE-627)ELV04924793X (ELSEVIER)S0006-291X(19)32342-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Rodrigues, Silvia D. verfasserin aut Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux 2020transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Oxidative stress Elsevier Uremic toxins Elsevier Protein carbonylation Elsevier Autophagy impairment Elsevier Chronic kidney disease Elsevier Santos, Sabrina S. oth Meireles, Tassiana oth Romero, Natalia oth Glorieux, Griet oth Pecoits-Filho, Roberto oth Zhang, Donna D. oth Nakao, Lia S. oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:523 year:2020 number:1 day:26 month:02 pages:123-129 extent:7 https://doi.org/10.1016/j.bbrc.2019.12.022 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 523 2020 1 26 0226 123-129 7 |
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10.1016/j.bbrc.2019.12.022 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000895.pica (DE-627)ELV04924793X (ELSEVIER)S0006-291X(19)32342-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Rodrigues, Silvia D. verfasserin aut Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux 2020transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. Oxidative stress Elsevier Uremic toxins Elsevier Protein carbonylation Elsevier Autophagy impairment Elsevier Chronic kidney disease Elsevier Santos, Sabrina S. oth Meireles, Tassiana oth Romero, Natalia oth Glorieux, Griet oth Pecoits-Filho, Roberto oth Zhang, Donna D. oth Nakao, Lia S. oth Enthalten in Academic Press Zhang, Zhikun ELSEVIER Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag 2019 BBRC Orlando, Fla (DE-627)ELV002811154 volume:523 year:2020 number:1 day:26 month:02 pages:123-129 extent:7 https://doi.org/10.1016/j.bbrc.2019.12.022 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 523 2020 1 26 0226 123-129 7 |
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Enthalten in Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag Orlando, Fla volume:523 year:2020 number:1 day:26 month:02 pages:123-129 extent:7 |
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Enthalten in Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag Orlando, Fla volume:523 year:2020 number:1 day:26 month:02 pages:123-129 extent:7 |
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Oxidative stress Uremic toxins Protein carbonylation Autophagy impairment Chronic kidney disease |
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Preparation and characterization of glass-ceramics via co-sintering of coal fly ash and oil shale ash-derived amorphous slag |
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Rodrigues, Silvia D. @@aut@@ Santos, Sabrina S. @@oth@@ Meireles, Tassiana @@oth@@ Romero, Natalia @@oth@@ Glorieux, Griet @@oth@@ Pecoits-Filho, Roberto @@oth@@ Zhang, Donna D. @@oth@@ Nakao, Lia S. @@oth@@ |
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Rodrigues, Silvia D. |
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Rodrigues, Silvia D. ddc 670 bkl 51.60 bkl 58.45 Elsevier Oxidative stress Elsevier Uremic toxins Elsevier Protein carbonylation Elsevier Autophagy impairment Elsevier Chronic kidney disease Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux |
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uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux |
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Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux |
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Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. |
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Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. |
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Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction. |
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