Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins
Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown....
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kim, Soojin [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018transfer 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 |
|---|---|
| Übergeordnetes Werk: |
volume:495 ; year:2018 ; number:1 ; day:1 ; month:01 ; pages:1541-1547 ; extent:7 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.bbrc.2017.11.202 |
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| 245 | 1 | 0 | |a Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins |
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| 520 | |a Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. | ||
| 520 | |a Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. | ||
| 650 | 7 | |a Bile acid |2 Elsevier | |
| 650 | 7 | |a Bile duct ligation |2 Elsevier | |
| 650 | 7 | |a Cholic acid |2 Elsevier | |
| 650 | 7 | |a Chenodeoxycholic acid |2 Elsevier | |
| 650 | 7 | |a Autophagosome |2 Elsevier | |
| 650 | 7 | |a Autophagy |2 Elsevier | |
| 700 | 1 | |a Han, Seung Yun |4 oth | |
| 700 | 1 | |a Yu, Kwang Sik |4 oth | |
| 700 | 1 | |a Han, Daewon |4 oth | |
| 700 | 1 | |a Ahn, Hyo-Ju |4 oth | |
| 700 | 1 | |a Jo, Jae-Eun |4 oth | |
| 700 | 1 | |a Kim, Jin-Hoi |4 oth | |
| 700 | 1 | |a Shin, Jongdae |4 oth | |
| 700 | 1 | |a Park, Hwan-Woo |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.2017.11.202 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001215.pica (DE-627)ELV041387007 (ELSEVIER)S0006-291X(17)32379-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Kim, Soojin verfasserin aut Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins 2018transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Bile acid Elsevier Bile duct ligation Elsevier Cholic acid Elsevier Chenodeoxycholic acid Elsevier Autophagosome Elsevier Autophagy Elsevier Han, Seung Yun oth Yu, Kwang Sik oth Han, Daewon oth Ahn, Hyo-Ju oth Jo, Jae-Eun oth Kim, Jin-Hoi oth Shin, Jongdae oth Park, Hwan-Woo 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:495 year:2018 number:1 day:1 month:01 pages:1541-1547 extent:7 https://doi.org/10.1016/j.bbrc.2017.11.202 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 495 2018 1 1 0101 1541-1547 7 |
| spelling |
10.1016/j.bbrc.2017.11.202 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001215.pica (DE-627)ELV041387007 (ELSEVIER)S0006-291X(17)32379-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Kim, Soojin verfasserin aut Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins 2018transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Bile acid Elsevier Bile duct ligation Elsevier Cholic acid Elsevier Chenodeoxycholic acid Elsevier Autophagosome Elsevier Autophagy Elsevier Han, Seung Yun oth Yu, Kwang Sik oth Han, Daewon oth Ahn, Hyo-Ju oth Jo, Jae-Eun oth Kim, Jin-Hoi oth Shin, Jongdae oth Park, Hwan-Woo 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:495 year:2018 number:1 day:1 month:01 pages:1541-1547 extent:7 https://doi.org/10.1016/j.bbrc.2017.11.202 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 495 2018 1 1 0101 1541-1547 7 |
| allfields_unstemmed |
10.1016/j.bbrc.2017.11.202 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001215.pica (DE-627)ELV041387007 (ELSEVIER)S0006-291X(17)32379-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Kim, Soojin verfasserin aut Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins 2018transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Bile acid Elsevier Bile duct ligation Elsevier Cholic acid Elsevier Chenodeoxycholic acid Elsevier Autophagosome Elsevier Autophagy Elsevier Han, Seung Yun oth Yu, Kwang Sik oth Han, Daewon oth Ahn, Hyo-Ju oth Jo, Jae-Eun oth Kim, Jin-Hoi oth Shin, Jongdae oth Park, Hwan-Woo 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:495 year:2018 number:1 day:1 month:01 pages:1541-1547 extent:7 https://doi.org/10.1016/j.bbrc.2017.11.202 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 495 2018 1 1 0101 1541-1547 7 |
| allfieldsGer |
10.1016/j.bbrc.2017.11.202 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001215.pica (DE-627)ELV041387007 (ELSEVIER)S0006-291X(17)32379-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Kim, Soojin verfasserin aut Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins 2018transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Bile acid Elsevier Bile duct ligation Elsevier Cholic acid Elsevier Chenodeoxycholic acid Elsevier Autophagosome Elsevier Autophagy Elsevier Han, Seung Yun oth Yu, Kwang Sik oth Han, Daewon oth Ahn, Hyo-Ju oth Jo, Jae-Eun oth Kim, Jin-Hoi oth Shin, Jongdae oth Park, Hwan-Woo 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:495 year:2018 number:1 day:1 month:01 pages:1541-1547 extent:7 https://doi.org/10.1016/j.bbrc.2017.11.202 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 495 2018 1 1 0101 1541-1547 7 |
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10.1016/j.bbrc.2017.11.202 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001215.pica (DE-627)ELV041387007 (ELSEVIER)S0006-291X(17)32379-3 DE-627 ger DE-627 rakwb eng 670 VZ 51.60 bkl 58.45 bkl Kim, Soojin verfasserin aut Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins 2018transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. Bile acid Elsevier Bile duct ligation Elsevier Cholic acid Elsevier Chenodeoxycholic acid Elsevier Autophagosome Elsevier Autophagy Elsevier Han, Seung Yun oth Yu, Kwang Sik oth Han, Daewon oth Ahn, Hyo-Ju oth Jo, Jae-Eun oth Kim, Jin-Hoi oth Shin, Jongdae oth Park, Hwan-Woo 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:495 year:2018 number:1 day:1 month:01 pages:1541-1547 extent:7 https://doi.org/10.1016/j.bbrc.2017.11.202 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 51.60 Keramische Werkstoffe Hartstoffe Werkstoffkunde VZ 58.45 Gesteinshüttenkunde VZ AR 495 2018 1 1 0101 1541-1547 7 |
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English |
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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:495 year:2018 number:1 day:1 month:01 pages:1541-1547 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:495 year:2018 number:1 day:1 month:01 pages:1541-1547 extent:7 |
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Bile acid Bile duct ligation Cholic acid Chenodeoxycholic acid Autophagosome Autophagy |
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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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Kim, Soojin @@aut@@ Han, Seung Yun @@oth@@ Yu, Kwang Sik @@oth@@ Han, Daewon @@oth@@ Ahn, Hyo-Ju @@oth@@ Jo, Jae-Eun @@oth@@ Kim, Jin-Hoi @@oth@@ Shin, Jongdae @@oth@@ Park, Hwan-Woo @@oth@@ |
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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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impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins |
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Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins |
| abstract |
Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. |
| abstractGer |
Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. |
| abstract_unstemmed |
Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA) and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and inflammatory response. However, the detailed mechanisms regarding the role of autophagy in cholestatic hepatotoxicity remain largely unknown. Here we determined autophagic clearance in livers of bile duct-ligated mice, in which bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and CA. The accumulation of bile acids caused defective autophagic clearance, shown by the accumulation of insoluble p62 and ubiquitinated proteins and cell death accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also showed the accumulation of autophagosomes via suppressed autophagy flux. Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the liver. Our data demonstrate that inhibited autophagy is an essential component of liver injury during cholestasis. |
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Han, Seung Yun Yu, Kwang Sik Han, Daewon Ahn, Hyo-Ju Jo, Jae-Eun Kim, Jin-Hoi Shin, Jongdae Park, Hwan-Woo |
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