Parkin deficiency elevates hepatic ischemia/reperfusion injury accompanying decreased mitochondrial autophagy, increased apoptosis, impaired DNA damage repair and altered cell cycle distribution

Ning,Xiao‑Jie; Yan,Xiong; Wang,Yan‑Feng; Wang,Ren; Fan,Xiao‑Li; Zhong,Zi‑Biao; Ye,Qi‑Fa

doi:10.3892/mmr.2018.9606

Parkin deficiency elevates hepatic ischemia/reperfusion injury accompanying decreased mitochondrial autophagy, increased apoptosis, impaired DNA damage repair and altered cell cycle distribution

Authors:
- Xiao‑Jie Ning
- Xiong Yan
- Yan‑Feng Wang
- Ren Wang
- Xiao‑Li Fan
- Zi‑Biao Zhong
- Qi‑Fa Ye
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Affiliations: Hubei Key Laboratory of Medical Technology on Transplantation, Institute of Hepatobiliary Diseases, Zhongnan Hospital of Wuhan University, Transplant Center of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: October 29, 2018 https://doi.org/10.3892/mmr.2018.9606
Pages: 5663-5668

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Abstract

Hepatic ischemia/reperfusion injury (HIRI) serves a causative role in postoperative hepatocyte death; however, the mechanisms underlying HIRI remain unclear. Mitochondrial autophagy, with apoptosis, cell cycle distribution and DNA damage repair, may be regarded as a regulatory factor post‑HIRI. Parkin, a novel ubiquitin ligase, has been reported to increase mitochondrial autophagy and decrease apoptosis. However, the association between Parkin, mitochondrial autophagy and other regulatory factors in HIRI is unclear. In the present study, the effects of Parkin on HIRI were investigated, using hepatocytes and livers from male Sprague Dawley rats subjected to simulated in vivo HIRI. The results of the present study demonstrated that Parkin expression and mitochondrial autophagy were upregulated post‑HIRI, leading to decreased hepatocyte death. Parkin knockdown suppresses the level of mitochondrial autophagy and promotes hepatocyte apoptosis by suppressing apoptosis regulator Bcl‑2 function post‑HIRI. In addition, Parkin deficiency alters cell cycle distribution and impairs DNA damage repair post‑HIRI. In conclusion, Parkin facilitates mitochondrial autophagy and DNA damage repair, inhibits apoptosis, and modulates the cell cycle, leading to increased hepatocyte survival, demonstrating that Parkin may act as a protective regulatory factor post HIRI.

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