PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation
| Autor: | Na Jiang, Xinghua Shao, Qisheng Lin, Minfang Zhang, Shu Li, Zhen Zhang, Haijiao Jin, Renhua Lu, Jianxiao Shen, Yijun Zhou, Leyi Gu, Zhaohui Ni, Wenyan Zhou |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Inflammasomes Ubiquitin-Protein Ligases Clinical Biochemistry Contrast Media Apoptosis PINK1 Mitochondrion urologic and male genital diseases Biochemistry Parkin Cell Line Kidney Tubules Proximal Mice 03 medical and health sciences 0302 clinical medicine NLR Family Pyrin Domain-Containing 3 Protein Mitophagy medicine Animals Humans lcsh:QH301-705.5 Mice Knockout chemistry.chemical_classification Reactive oxygen species lcsh:R5-920 Organic Chemistry Acute kidney injury Epithelial Cells Acute Kidney Injury medicine.disease Mitochondria Cell biology Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation chemistry lcsh:Biology (General) Reactive Oxygen Species lcsh:Medicine (General) Protein Kinases 030217 neurology & neurosurgery Research Paper Signal Transduction |
| Zdroj: | Redox Biology, Vol 26, Iss, Pp-(2019) |
| ISSN: | 2213-2317 |
| Popis: | Contrast-induced acute kidney injury (CI-AKI) occurs in more than 30% of patients after intravenous iodinated contrast media and causes serious complications, including renal failure and mortality. Recent research has demonstrated that routine antioxidant and alkaline therapy failed to show benefits in CI-AKI patients with high risk for renal complications. Mitophagy is a mechanism of selective autophagy, which controls mitochondrial quality and mitochondrial reactive oxygen species (ROS) through degradation of damaged mitochondria. The role of mitophagy and its regulation of apoptosis in CI-AKI are poorly understood. In this study, we demonstrated that mitophagy was induced in renal tubular epithelial cells (RTECs) during CI-AKI, both in vivo and in vitro. Meanwhile, contrast media–induced mitophagy was abolished when silencing PINK1 or PARK2 (Parkin), indicating a dominant role of the PINK1-Parkin pathway in mitophagy. Moreover, mitochondrial damage, mitochondrial ROS, RTEC apoptosis, and renal injury under contrast exposure were more severe in PINK1- or PARK2-deficient cells and mice than in wild-type groups. Functionally, PINK1-Parkin–mediated mitophagy prevented RTEC apoptosis and tissue damage in CI-AKI through reducing mitochondrial ROS and subsequent NLRP3 inflammasome activation. These results demonstrated that PINK1-Parkin–mediated mitophagy played a protective role in CI-AKI by reducing NLRP3 inflammasome activation. Keywords: Acute kidney injury, Contrast media, Mitophagy, Mitochondrial ROS, NLRP3 inflammasome, Apoptosis |
| Databáze: | OpenAIRE |
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