Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury

Abstract

Background/Aims: Contrast induced-acute kidney injury (CI-AKI) is one of the most common causes of acute kidney injury (AKI) in hospitalized patients. Mitophagy, the selective elimination of mitochondria via autophagy, is an important mechanism of mitochondrial quality control in physiological and pathological conditions. In this study, we aimed to determine effects of iohexol and iodixanol on mitochondrial reactive oxygen species (ROS), mitophagy and the potential role of mitophagy in CI-AKI cell models. Methods: Cell viability was measured by cell counting kit-8. Cell apoptosis, mitochondrial ROS and mitochondrial membrane potential were detected by western blot, MitoSOX fluorescence and TMRE staining respectively. Mitophagy was detected by the colocalization of LC3-FITC with MitoTracker Red, western blot and electronic microscope. Results: The results showed that mitophagy was induced in human renal tubular cells (HK-2 cells) under different concentrations of iodinated contrast media. Mitochondrial ROS displayed increased expression after the treatment. Rapamycin (Rap) enhanced mitophagy and alleviated contrast media induced HK-2 cells injury. In contrast, autophagy inhibitor 3-methyladenine (3-MA) down-regulated mitophagy and aggravated cells injury. Conclusions: Together, our finding indicates that iohexol and iodixanol contribute to the generation of mitochondrial ROS and mitophagy. The enhancement of mitophagy can effectively protect the kidney from iodinated contrast (iohexol)-induced renal tubular epithelial cells injury.

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

“…Since oxidative stress is closely related with mitophagy [24], and mitophagy protects cells from apoptosis under environmental stress [25, 26]. We next explore whether high glucose inhibits RPE proliferation and promotes cell apoptosis by regulating oxidative stress mediated mitophagy.…”

Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

“…Blotting. Cells or renal cortical tissues (n = 3 from each group) were isolated, as described previously [6,7]. Nuclear and cytoplasm protein were extracted according to the operating instructions.…”

“…Determination of Reactive Oxygen Species. Mitochondrial ROS in HK-2 cells was evaluated by using MitoSOX Red (Invitrogen Corporation, USA) as previously described [7], according to the manufacturer's instruction. Briefly, cells growing in cell culture plates were rinsed and incubated in MitoSOX (Invitrogen Corporation, USA) for 8 minutes at 37°C in the dark.…”

“…Many pathophysiological processes contribute to the development of CI-AKI, such as renal medullary ischemia, direct tubular cytotoxicity of contrast, overproduction of reactive oxygen species (ROS), mitochondrial damage, and mitophagy [1,[6][7][8][9]. Most guidelines suggest that expanding intravascular volume is more reasonable in preventing CI-AKI [10,11].…”

Ethanol-activated CaMKII signaling induces neuronal apoptosis through Drp1-mediated excessive mitochondrial fission and JNK1-dependent NLRP3 inflammasome activation.

“…Although many researchers have shown the protective role of mitophagy in oxidative stress, mitochondrial dysfunction, and apoptosis [56,57], the regulation of mitophagy in an ethanol environment is still controversial. We found that ethanol-activated caspase-1 plays a key role in parkin-mediated mitophagy and neuronal apoptosis.…”