Ox‐LDL aggravates contrast‐induced injury of renal tubular epithelial cells.

Autor: Yang, Dingwei, Yang, Xueyan, Chen, Sha, Lv, Meiling, Tan, Jin, Yang, Dingping
Předmět:
Zdroj: Journal of Biochemical & Molecular Toxicology; Aug2023, Vol. 37 Issue 8, p1-12, 12p
Abstrakt: Hypercholesterolemia can aggravate contrast‐induced acute kidney injury, and the exacerbation of renal tubular epithelial cell (RTEC) injury is a major cause. However, the exact mechanisms remain obscure. Mitophagy, a type of autophagy, selectively eliminates damaged mitochondria and reduces mitochondrial oxidative stress, which is strongly implicated in cell homeostasis and acute kidney injury. Oxidized low‐density lipoprotein (Ox‐LDL) is accumulated in hypercholesterolemia and has a cytotoxic effect. This study aimed to determine whether and how ox‐LDL exacerbates contrast‐induced injury in RTECs and to further explore whether PINK1/Parkin‐dependent mitophagy is involved in this process. Iohexol and ox‐LDL were used alone or in combination to treat HK‐2 cells. Rapamycin pretreatment was utilized to enhance mitophagy. Cell viability, apoptosis, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS) were detected by cell counting kit‐8, TUNEL staining, JC‐1 kit and MitoSOX fluorescence, respectively. The expression of mitophagy‐related proteins (including PINK1, Parkin, and so on) and cleaved caspase‐3 was confirmed by western blot. Colocalization of MitoTracker‐labeled mitochondria and LysoTracker‐labeled lysosomes was observed by fluorescence microscopy to evaluate mitophagy. The results of our study showed that ox‐LDL aggravated MMP decline, mtROS release and apoptosis in iohexol‐treated HK‐2 cells, accompanied by a further increased autophagy level. Enhancement of PINK1/Parkin‐dependent mitophagy by rapamycin alleviated apoptosis and mitochondrial injury in HK‐2 cells in response to iohexol under ox‐LDL condition. Therefore, our findings indicate that ox‐LDL aggravates contrast‐induced injury of RTECs by increasing mitochondrial damage and mitochondrial oxidative stress, which may be associated with the relative insufficiency of PINK1/Parkin‐dependent mitophagy. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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