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Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

Hypoxia is a kind of common pathological condition existing in various diseases such as sleep apnea syndrome, myocardial infarction and stroke, which can precipitate the onset of diseases through inducing cell apoptosis. Ca2+ is the ubiquitous message in cell. Given the crucial role of Ca2+ in physiology, intracellular Ca2+ overload is a significant regulator of apoptosis. Numerous experiments show that hypoxia may cause changes of multiple cellular Ca2+ channels, for instance, Na+/Ca2+ Exchanger (NCX), L-type voltage dependent Ca2+ channel (L-VDCC), inositol triphosphate receptors (IP3R) and so on, which contribute to intracellular Ca2+ overload, thus eventually triggering cell apoptosis. However, the mechanisms underlying different Ca2+ channels involved in hypoxic apoptosis are complex. For example, chronic hypoxia or acute hypoxia may select different Ca2+ channels to influence cell apoptosis. In addition, intracellular Ca2+ overload may initiate different apoptotic pathways due to hypoxic duration. Furthermore, different locations in the cell of specific Ca2+ channels activated by hypoxia will determine different apoptosis signaling pathways. Moreover, activation of different Ca2+ channel isoforms will result in different outcomes of the cell under hypoxia. Hence, we aim to highlight the potential mechanisms of the main Ca2+ channels in regulation of apoptosis under hypoxic stress.