Salusin-? mediates tubular cell apoptosis in acute kidney injury: Involvement of the PKC/ROS signaling pathway.

ABSTRACT: Salusin-? is abundantly expressed in many organs and tissues including heart, blood vessels, brain and kidneys. Recent studies have identified salusin-? as a bioactive peptide that contributes to various diseases, such as atherosclerosis, hypertension, diabetes and metabolic syndrome. However, the role of salusin-? in the pathogenesis of acute kidney injury (AKI) is largely unclear. In the present study, we investigated the roles of salusin-? in cisplatin or lipopolysaccharide (LPS)-induced renal injury. Herein, we found that salusin-? expression was upregulated in both renal tubular cells and kidney tissues induced by both cisplatin and LPS. In vitro, silencing of salusin-? diminished, whereas overexpression of salusin-? exaggerated the increased PKC phosphorylation, oxidative stress, histone ?H2AX expression, p53 activation and apoptosis in either cisplatin or LPS-challenged renal tubular cells. More importantly, salusin-? overexpression-induced tubular cell apoptosis were abolished by using the PKC inhibitor Go 6976, reactive oxygen species (ROS) scavenger NAC, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin (Apo) or p53 inhibitor Pifithrin-?. In animals, blockade of salusin-? alleviated PKC phosphorylation, ROS accumulation, DNA damage, and p53 activation as well as renal dysfunction in mice after administration of cisplatin or LPS. Taken together, these results suggest that overexpressed salusin-? is deleterious in AKI by activation of the PKC/ROS signaling pathway, thereby priming renal tubular cells for apoptosis and death.

SUBMITTER: Lu QB 

PROVIDER: S-EPMC6939056 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature