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TAK1 is involved in sodium L-lactate-stimulated p38 signaling and promotes apoptosis

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A Correction to this article was published on 22 May 2021

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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.

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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

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

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Acknowledgements

This work was supported by the basic and applied basic research project of Guangdong (Youth fund projects, 2019A1515110111); the science and technology development project of Guangdong (2017B090904010); the Shenzhen municipal commission of health and family planning (No. SZFZ2018071); and Chen xiaoping academician workstation of hepatobiliary surgery, Peking University shenzhen hospital, guangdong province.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University, The Hong Kong University of Science and Technology Medical Center, Shenzhen, China

    Qingen Da, Zilong Yan, Zhangfu Li & Jikui Liu

  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

    Qingen Da, Zhen Han, Mingming Ren, Lei Huang & Tao Wang

  3. School of Basic Medical Sciences, Peking University, Beijing, China

    Xiaowei Zhang

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  1. Qingen Da
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Contributions

QD, ZH, MR, XZ, JL, and TW designed research; QD, ZY, ZL, and LH performed experiments; QD, ZH, LH, JL, and TW analyzed data; QD, ZH, MR, XZ, JL, and TW wrote and revised the manuscript; QD, ZY, ZL, and LH provided the reagents or materials and participated in experimental design.

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Correspondence to Jikui Liu or Tao Wang.

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Da, Q., Yan, Z., Li, Z. et al. TAK1 is involved in sodium L-lactate-stimulated p38 signaling and promotes apoptosis. Mol Cell Biochem 476, 873–882 (2021). https://doi.org/10.1007/s11010-020-03952-y

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