TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53

Na-Rae Joo; Sang-Ah Park; Jung-Hwan Park; Sang-Muk Oh

doi:10.1016/j.bbrc.2023.04.113

TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53

Biochem Biophys Res Commun. 2023 Jul 5:664:128-135. doi: 10.1016/j.bbrc.2023.04.113. Epub 2023 Apr 29.

Authors

Na-Rae Joo¹, Sang-Ah Park¹, Jung-Hwan Park², Sang-Muk Oh³

Affiliations

¹ Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea.
² Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea. Electronic address: zerro21@hanmail.net.
³ Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea; Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, 35365, South Korea. Electronic address: sangmuk_oh@konyang.ac.kr.

PMID: 37148702
DOI: 10.1016/j.bbrc.2023.04.113

Abstract

T-LAK cell originated protein kinase (TOPK) has been shown to regulate proliferation, invasion or migration of various cancer cells. However, the role of TOPK in follicle environments remains unknown. Here we reveal that TOPK inhibits TNF-α-induced human granulosa COV434 cell apoptosis. The expression of TOPK were increased in COV434 cells in response to TNF-α. TOPK inhibition also decreased TNF-α-induced SIRT1 expression but promoted TNF-α-induced p53 acetylation and expression of PUMA or NOXA. Accordingly, TOPK inhibition attenuated TNF-α-mediated SIRT1 transcriptional activity. In addition, SIRT1 inhibition augmented acetylation of p53 or expression of PUMA and NOXA in response to TNF-α, leading to COV434 cell apoptosis. We conclude that TOPK suppresses TNF-α-induced COV434 granulosa cell apoptosis via regulation of p53/SIRT1 axis, suggesting a potential role of TOPK in regulation of ovarian follicular development.

Keywords: Apoptosis; Granulosa cell; TNF-α; TOPK.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / metabolism
Apoptosis* / physiology
Extracellular Signal-Regulated MAP Kinases / metabolism
Female
Granulosa Cells* / metabolism
Humans
Mitogen-Activated Protein Kinase Kinases / metabolism
Sirtuin 1 / genetics
Sirtuin 1 / metabolism
Tumor Necrosis Factor-alpha* / metabolism
Tumor Necrosis Factor-alpha* / pharmacology
Tumor Suppressor Protein p53* / metabolism

Substances

Apoptosis Regulatory Proteins
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase Kinases
SIRT1 protein, human
Sirtuin 1
Tumor Necrosis Factor-alpha
Tumor Suppressor Protein p53