SOCS-1 is involved in TNF-α-induced mitochondrial dysfunction and apoptosis in renal tubular epithelial cells. Issue 5 (October 2017)

• Record Type: Journal Article
• Authors: Du, Chunyang; Yao, Fang; Ren, Yunzhuo; Du, Yunxia; Wei, Jinying; Wu, Haijiang; Duan, Huijun; Shi, Yonghong
• Is Part Of: Tissue & cell. Volume 49:Issue 5(2017)
• Page Start: 537
• Page End: 544
• Publication Date: 2017-10
• Subjects: TNF-α tumor necrosis factor-α -- CKD chronic kidney disease -- ESRD end-stage renal disease -- SOCS-1 suppressor of cytokine signaling-1 -- HKCs human renal tubular epithelial cells -- ASK1 apoptosis signal regulating kinase-1 -- RTEC renal tubular epithelial cell -- cyt c cytochrome c -- NOX4 NADPH oxidase 4 -- SOD2 superoxide dismutase 2 -- LIF leukemia-inhibitory factor; Apoptosis -- SOCS-1 -- TNF-α -- HKC -- Mitochondrial dysfunction; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2017.06.005
• Languages: English
• ISSNs: 0040-8166

Abstract

Highlights: TNF-α induced expression of SOCS-1. Overexpression of SOCS-1 inhibited mitochondrial dysfunction, oxidative stress and apoptosis induced by TNF-α. Overexpression of SOCS-1 inhibited activation of JAK/STAT signaling pathway induced by TNF-α. Abstract: Tumor necrosis factor-α (TNF-α) is suggested to induce mitochondrial dysfunction and apoptosis of renal tubular epithelial cells that possibly exacerbates renal function in chronic kidney disease (CKD). Here we investigated whether suppressor of cytokine signaling-1 (SOCS-1), an inhibitor of cytokine signaling, was involved in TNF-α-induced human renal tubular epithelial cells (HKCs) oxidative stress and apoptosis. TNF-α promoted the protein and mRNA expression of SOCS-1 in a time and dose dependent manner, along with increased cell apoptosis and activation of apoptosis signal regulating kinase-1(ASK1) in HKCs. Furthermore, overexpression of SOCS-1 in HKCs reduced TNF-α-mediated oxidative stress and apoptosis. Meanwhile, We also found that overexpression of SOCS-1 could regulate the activity of JAK/STAT signaling pathway. In addition, a specific JAK2 inhibitor, AG490, that both attenuated TNF-α-induced oxidative stress, also reduced apoptosis. Taken together, overexpression of SOCS-1 prevented TNF-α-mediated cell oxidative stress and apoptosis may be via suppression of JAK/STAT signaling pathway activation in HKCs.