Relaxin Attenuates Contrast-Induced Human Proximal Tubular Epithelial Cell Apoptosis by Activation of the PI3K/Akt Signaling Pathway In Vitro

Abstract

Background. Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited. This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms. Methods. Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway). Cell viability was evaluated with a CCK-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 staining method. Apoptosis was detected with Annexin V staining. Western blot analysis was employed to measure the expression of pAkt (S473), Akt, cleaved caspase-3, Bcl-2, Bax, and actin proteins. Results. Ioversol reduced the viability of HK-2 cells. Western blotting results revealed decreased expression of phosphorylated Akt in cells treated with ioversol. The activities of caspase-3 and Bax protein increased, while the expression of Bcl-2 protein decreased. As a result, the Bax/Bcl-2 ratio increased after treatment with ioversol. These effects were reversed when HK-2 cells were cotreated with RLX. However, with preadministration of PI3K/Akt pathway inhibitor LY294002, the effect of RLX was blocked. Conclusion. Our study demonstrates that relaxin attenuates ioversol induced cell apoptosis via activation of the PI3K/Akt signaling pathway, suggesting that RLX might play a protective role in the treatment of CI-AKI.

Extracts of Artocarpus communis Induce Mitochondria-Associated Apoptosis via Pro-oxidative Activity in Human Glioblastoma Cells

“…In this study, phosphorylation of S473 in Akt occurred during artocarpin-mediated apoptosis. This reaction was reported previously ( Hsieh et al, 2010 ; Tsai et al, 2017 ; Xie et al, 2017 ). In the present study, we observed that artocarpin induced Akt activation in glioblastoma cells.…”

“…Both NADPH and NADH contributed to the background of the lucigenin chemiluminescence ( James et al, 2005 ; Manning and Cantley, 2007 ; Sahu et al, 2009 ; Hsieh et al, 2010 ; Kim et al, 2013 ; Savitskaya and Onishchenko, 2015 ; Chen Z.P. et al, 2016 ; Lee et al, 2017 ; Tsai et al, 2017 ; Xie et al, 2017 ) counts per min). Chemiluminescence was measured continuously for 12 min and expressed in the standard units of NADPH oxidase activity.…”

Contrast Induced Acute Kidney Injury and Direct Cytotoxicity of Iodinated Radiocontrast Media on Renal Proximal Tubule Cells

“…Additional kinases important to cellular survival that are affected by RCM exposure include protein kinase B, PTEN-induced putative kinase, Rho-associated protein kinase (ROCK), Janus kinases (JAKs), and signal transducer and activator of transcription (STAT) proteins. A study performed by Xie et al (2017) on the effects of ioversol on HK-2 cells indicated that 30-minute exposure to 100 mg/ml of ioversol significantly decreases the presence of phosphorylated protein kinase B while simultaneously inducing caspase-3 cleavage and apoptosis. This discovery demonstrates that the phosphoinositide-3 kinase/protein kinase B pathway may play a role in cellular fate after exposure to RCM.…”

Total Flavonoids from Oroxylum indicum Induce Apoptosis via PI3K/Akt/PTEN Signaling Pathway in Liver Cancer

“…The Bax gene is a tumor suppressor gene, and Bcl-2 is an antiapoptotic gene that antagonizes the function of Bax [ 26 , 27 ]. Moreover, Caspase-3 is the main process in the induction of apoptosis, since it is activated to regulate the caspase-signaling cascade and a downstream effector of apoptosis pathways [ 28 ]. In this study, the results of HE straining and flow cytometry showed that apoptosis occurred both in tumor tissues and in SMMC-7721 cells after TF intervention.…”