Influence of Fat on Differential Receptor Interacting Serine/Threonine Protein Kinase 1 Activity Leading to Apoptotic Cell Death in Murine Liver Ischemia Reperfusion Injury Through Caspase 8

The female sex has been associated with improved myocardial salvage after ischemia and reperfusion (I/R). Estrogen, specifically 17β-estradiol, has been demonstrated to mediate this phenomenon by limiting cardiomyocyte apoptosis. We sought to quantitatively assess the effect of sex, ovarian hormone loss, and I/R on myocardial Bax, Bcl-2, and apoptosis repressor with caspase recruitment domain (ARC) expression. Male ( n = 48), female ( n = 26), and oophorectomized female ( n = 20) rabbits underwent 30 min of regional ischemia and 3 h of reperfusion. The myocardial area at risk and infarct size were determined using a double-staining technique and planimetry. In situ oligo ligation was used to assess apoptotic cell death. Western blot analysis was used to determine proapoptotic (Bax) and antiapoptotic (Bcl-2 and ARC) protein levels in all three ischemic groups and, additionally, in three nonischemic groups. Infarct size (43.7 ± 3.2%) and apoptotic cell death (0.51 ± 0.10%) were significantly attenuated in females compared with males (56.4 ± 1.6%, P < 0.01, and 4.29 ± 0.95%, P < 0.01) and oophorectomized females (55.7 ± 3.4%, P < 0.05, and 4.36 ± 0.51%, P < 0.01). Females expressed significantly higher baseline ARC levels (3.62 ± 0.29) compared with males (1.78 ± 0.18, P < 0.01) and oophorectomized females (1.08 ± 0.26, P < 0.01). Males expressed a significantly higher baseline Bax-to-Bcl-2 ratio (4.32 ± 0.99) compared with females (0.65 ± 0.13, P < 0.01) and oophorectomized females (0.42 ± 0.10, P < 0.01). I/R significantly reduced Bax-to-Bcl-2 ratios in males. In all other groups, ARC levels and Bax-to-Bcl-2 ratios did not significantly change. These results support the conclusion that in females, endogenous estrogen limits I/R-induced cardiomyocyte apoptosis by producing a baseline antiapoptotic profile, which is associated with estrogen-dependent high constitutive myocardial ARC expression.

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Vasoactive intestinal peptide attenuates liver ischemia/reperfusion injury in mice via the cyclic adenosine monophosphate-protein kinase a pathway

Liver Transplantation ◽

10.1002/lt.23681 ◽

2013 ◽

Vol 19 (9) ◽

pp. 945-956 ◽

Cited By ~ 7

Author(s):

Haofeng Ji ◽

Yu Zhang ◽

Yuanxing Liu ◽

Xiu-Da Shen ◽

Feng Gao ◽

...

Keyword(s):

Protein Kinase ◽

Reperfusion Injury ◽

Protein Kinase A ◽

Vasoactive Intestinal Peptide ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Liver Ischemia ◽

Kinase A

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Autophagy and Liver Ischemia-Reperfusion Injury

BioMed Research International ◽

10.1155/2015/417590 ◽

2015 ◽

Vol 2015 ◽

pp. 1-16 ◽

Cited By ~ 47

Author(s):

Raffaele Cursio ◽

Pascal Colosetti ◽

Jean Gugenheim

Keyword(s):

Cell Death ◽

Hemorrhagic Shock ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Liver Ischemia ◽

Main Mode ◽

Patient Morbidity ◽

Diseased Liver

Liver ischemia-reperfusion (I-R) injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS), leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

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