Cholestasis confers resistance to the rat liver mitochondrial permeability transition

M. J. Liesee, J. Park, S. Natori, B. A. Jones, S. F. Bronk, Gregory James Gores

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Background and Aims: Bile salts can cause hepatocyte death by inducing the mitochondrial permeability transition (MPT). However, the slow progression of human cholestatic liver diseases suggests that hepatocytes adapt to resist the MPT. Bcl-x, a protein, and increased mitochondrial cardiolipin, a membrane lipid, elevate the threshold for the MPT. Our aims were to determine if liver mitochondria become resistant to the MPT during cholestasis and, if so, if the resistance is mediated by Bcl-x and/or increased cardiolipin. Methods: Hepatocytes and liver mitochondria were obtained from bile duct-ligated (BDL) rats and sham-operated rats (control). Results: After addition of glycochenodeoxycholate (GCDC), the magnitude of the MPT was reduced in mitochondria from BDL rats vs. controls. Although Bcl- x(L) was not increased, mitochondrial cardiolipin content was significantly greater in BDL rats vs. controls. Cell viability was also increased in hepatocytes from BDL rats vs. controls after treatment with GCDC. Feeding BDL rats a fatty acid-deficient diet prevented the increase in mitochondrial cardiolipin content; mitochondria and hepatocytes from these rats were susceptible to the MPT and hepatocellular death by GCDC. Conclusions: These data suggest that an increase in mitochondria cardiolipin content occurs during cholestasis as an adaptive phenomenon to resist cell death by the MPT.

Original languageEnglish (US)
Pages (from-to)693-701
Number of pages9
JournalGastroenterology
Volume115
Issue number3
StatePublished - 1998

Fingerprint

Cholestasis
Cardiolipins
Permeability
Bile Ducts
Glycochenodeoxycholic Acid
Hepatocytes
Liver
Mitochondria
Liver Mitochondrion
Mitochondrial Proteins
Membrane Lipids
Bile Acids and Salts
Liver Diseases
Cause of Death
Cell Survival
Cell Death
Fatty Acids
Diet

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Liesee, M. J., Park, J., Natori, S., Jones, B. A., Bronk, S. F., & Gores, G. J. (1998). Cholestasis confers resistance to the rat liver mitochondrial permeability transition. Gastroenterology, 115(3), 693-701.

Cholestasis confers resistance to the rat liver mitochondrial permeability transition. / Liesee, M. J.; Park, J.; Natori, S.; Jones, B. A.; Bronk, S. F.; Gores, Gregory James.

In: Gastroenterology, Vol. 115, No. 3, 1998, p. 693-701.

Research output: Contribution to journalArticle

Liesee, MJ, Park, J, Natori, S, Jones, BA, Bronk, SF & Gores, GJ 1998, 'Cholestasis confers resistance to the rat liver mitochondrial permeability transition', Gastroenterology, vol. 115, no. 3, pp. 693-701.
Liesee, M. J. ; Park, J. ; Natori, S. ; Jones, B. A. ; Bronk, S. F. ; Gores, Gregory James. / Cholestasis confers resistance to the rat liver mitochondrial permeability transition. In: Gastroenterology. 1998 ; Vol. 115, No. 3. pp. 693-701.
@article{32d752ba050c447d812f0aba66471762,
title = "Cholestasis confers resistance to the rat liver mitochondrial permeability transition",
abstract = "Background and Aims: Bile salts can cause hepatocyte death by inducing the mitochondrial permeability transition (MPT). However, the slow progression of human cholestatic liver diseases suggests that hepatocytes adapt to resist the MPT. Bcl-x, a protein, and increased mitochondrial cardiolipin, a membrane lipid, elevate the threshold for the MPT. Our aims were to determine if liver mitochondria become resistant to the MPT during cholestasis and, if so, if the resistance is mediated by Bcl-x and/or increased cardiolipin. Methods: Hepatocytes and liver mitochondria were obtained from bile duct-ligated (BDL) rats and sham-operated rats (control). Results: After addition of glycochenodeoxycholate (GCDC), the magnitude of the MPT was reduced in mitochondria from BDL rats vs. controls. Although Bcl- x(L) was not increased, mitochondrial cardiolipin content was significantly greater in BDL rats vs. controls. Cell viability was also increased in hepatocytes from BDL rats vs. controls after treatment with GCDC. Feeding BDL rats a fatty acid-deficient diet prevented the increase in mitochondrial cardiolipin content; mitochondria and hepatocytes from these rats were susceptible to the MPT and hepatocellular death by GCDC. Conclusions: These data suggest that an increase in mitochondria cardiolipin content occurs during cholestasis as an adaptive phenomenon to resist cell death by the MPT.",
author = "Liesee, {M. J.} and J. Park and S. Natori and Jones, {B. A.} and Bronk, {S. F.} and Gores, {Gregory James}",
year = "1998",
language = "English (US)",
volume = "115",
pages = "693--701",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Cholestasis confers resistance to the rat liver mitochondrial permeability transition

AU - Liesee, M. J.

AU - Park, J.

AU - Natori, S.

AU - Jones, B. A.

AU - Bronk, S. F.

AU - Gores, Gregory James

PY - 1998

Y1 - 1998

N2 - Background and Aims: Bile salts can cause hepatocyte death by inducing the mitochondrial permeability transition (MPT). However, the slow progression of human cholestatic liver diseases suggests that hepatocytes adapt to resist the MPT. Bcl-x, a protein, and increased mitochondrial cardiolipin, a membrane lipid, elevate the threshold for the MPT. Our aims were to determine if liver mitochondria become resistant to the MPT during cholestasis and, if so, if the resistance is mediated by Bcl-x and/or increased cardiolipin. Methods: Hepatocytes and liver mitochondria were obtained from bile duct-ligated (BDL) rats and sham-operated rats (control). Results: After addition of glycochenodeoxycholate (GCDC), the magnitude of the MPT was reduced in mitochondria from BDL rats vs. controls. Although Bcl- x(L) was not increased, mitochondrial cardiolipin content was significantly greater in BDL rats vs. controls. Cell viability was also increased in hepatocytes from BDL rats vs. controls after treatment with GCDC. Feeding BDL rats a fatty acid-deficient diet prevented the increase in mitochondrial cardiolipin content; mitochondria and hepatocytes from these rats were susceptible to the MPT and hepatocellular death by GCDC. Conclusions: These data suggest that an increase in mitochondria cardiolipin content occurs during cholestasis as an adaptive phenomenon to resist cell death by the MPT.

AB - Background and Aims: Bile salts can cause hepatocyte death by inducing the mitochondrial permeability transition (MPT). However, the slow progression of human cholestatic liver diseases suggests that hepatocytes adapt to resist the MPT. Bcl-x, a protein, and increased mitochondrial cardiolipin, a membrane lipid, elevate the threshold for the MPT. Our aims were to determine if liver mitochondria become resistant to the MPT during cholestasis and, if so, if the resistance is mediated by Bcl-x and/or increased cardiolipin. Methods: Hepatocytes and liver mitochondria were obtained from bile duct-ligated (BDL) rats and sham-operated rats (control). Results: After addition of glycochenodeoxycholate (GCDC), the magnitude of the MPT was reduced in mitochondria from BDL rats vs. controls. Although Bcl- x(L) was not increased, mitochondrial cardiolipin content was significantly greater in BDL rats vs. controls. Cell viability was also increased in hepatocytes from BDL rats vs. controls after treatment with GCDC. Feeding BDL rats a fatty acid-deficient diet prevented the increase in mitochondrial cardiolipin content; mitochondria and hepatocytes from these rats were susceptible to the MPT and hepatocellular death by GCDC. Conclusions: These data suggest that an increase in mitochondria cardiolipin content occurs during cholestasis as an adaptive phenomenon to resist cell death by the MPT.

UR - http://www.scopus.com/inward/record.url?scp=0031708617&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031708617&partnerID=8YFLogxK

M3 - Article

C2 - 9721167

AN - SCOPUS:0031708617

VL - 115

SP - 693

EP - 701

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -