TAK1 is involved in sodium L-lactate-stimulated p38 signaling and promotes apoptosis
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TAK1 is involved in sodium L‑lactate‑stimulated p38 signaling and promotes apoptosis Qingen Da1,2 · Zilong Yan1 · Zhangfu Li1 · Zhen Han2 · Mingming Ren2 · Lei Huang2 · Xiaowei Zhang3 · Jikui Liu1 · Tao Wang2 Received: 26 April 2020 / Accepted: 15 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In the present study, we found that the phosphorylation of p38 mitogen-activated protein kinase (p38) was significantly increased in L-lactate-treated HeLa cells, which is under concentration- and time-dependent manner. The protein level of Bcl-2 was significantly reduced and Bax and C-caspase3 were significantly increased in L-lactate-treated cells. qRT-PCR analysis suggested that the expression level of apoptosis-related genes Bax, C-myc, and FasL were significantly upregulated by L-lactate treatment. In addition, p38 inhibitor SB203580 blocked the L-lactate-stimulated phosphorylation of p38 (p-p38) and apoptosis, which suggested that L-lactate-stimulated apoptosis may be related to the activation of p38. Moreover, TAK1 inhibitor Takinib reduced L-lactate-triggered phosphorylation of p38 and also apoptosis; however, ASK1 inhibitor NQDI-1 did not. Cells transfected with siRNA of TAK1(siTAK1) showed similar results with Takinib inhibitor. These results suggested that the L-lactate treatment elevated activation of p38 and apoptosis was related to TAK1. In this study, we suggested that TAK1 plays an important role in L-lactate-stimulated activation of p38 affecting apoptosis in HeLa cells. Keywords L-lactate · Apoptosis · TAK1 · p38 Abbreviations L-Lactate Sodium L-Lactate PCD The programmed cell death MAPK Mitogen-activated protein kinase MAP3Ks MAP2K kinases p38 p38 mitogen-activated protein kinase p-p38 phosphorylated p38 ERK Extracellular signal-regulated kinases
* Jikui Liu [email protected] * Tao Wang [email protected] 1
Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University, The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
2
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University, The Hong Kong University of Science and Technology Medical Center, Shenzhen 518000, China
3
School of Basic Medical Sciences, Peking University, Beijing, China
JNK/SAPK c-jun N-terminal or stress-activated protein kinases Bcl-2 BCL-2 apoptosis regulator Bcl-xl BCL-2 like 1 Mcl1 Mcl1 apoptosis regulator Bcl-B BCL-2 like 10 Bax BCL-2associated X, apoptosis regulator Fas Fas cell surface death receptor FasL Fas ligand ASK1 Apoptosis signal-regulating kinase 1 TAK1 TGF (transforming growth factor) β-activated kinase 1
Introduction Apoptosis is the process by which the cells enters a process that ultimately results in the controlled death of the cell [1, 2]. The process of apoptosis is highly conserved, and the main cascade of events is regulated by the Bcl-2 gene family. The Bcl-2 gene family is mainly located in the outer mitochondrial membrane,
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