NOX4 deficiency improves the impaired viability, inhibited the apoptosis and suppressed autophagy of DHEA-treated ovarian granulosa cells through inhibiting endoplasmic reticulum stress via inactivating PERK/ATF4 pathway

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2024-11-28 DOI:10.1016/j.tice.2024.102640

Na Yu , Lingyuan Wu , Xin Xing

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引用次数: 0

Abstract

Background

PCOS is the most prevalent endocrine and metabolic problem in women of reproductive age. This current study was formulated to thoroughly expound the ovary-protecting effects of NOX4 deficiency in PCOS and probe into the intrinsic mechanisms underlying the protective effects of NOX4 deficiency against DHEA injury in ovarian GCs.

Methods

KGN cells were subjected to 20 nM DHEA for 48 h to establish PCOS cellular model. For loss-of-function experiments, KGN cells were transfected with si-NOX4. In addition, to investigate the biological roles of ERS and PERK/ATF4 pathway in the ovary-protecting effects of NOX4 deficiency in DHEA-treated ovarian GCs, KGN cells were pretreated with ERS agonist TM or PERK agonist CCT020312.

Results

NOX4 was highly expressed in DHEA-treated ovarian GCs. NOX4 deficiency improved the impaired viability, inhibited the apoptosis and suppressed autophagy of DHEA-treated ovarian GCs. Besides, NOX4 deficiency inactivated PERK/ATF4 pathway in DHEA-treated ovarian GCs. NOX4 deficiency repressed DHEA-induced ERS of ovarian GCs through inactivating PERK/ATF4 pathway. Pretreatment with ERS agonist TM or pretreatment with PERK agonist CCT020312 can both reduced the viability, promoted the apoptosis and strengthened autophagy of ovarian GCs, partially abolishing the ovary-protecting effects of NOX4 deficiency in DHEA-treated ovarian GCs. In general, NOX4 deficiency could improve the impaired viability, inhibited the apoptosis and suppressed autophagy of DHEA-treated ovarian GCs through repressing ERS depending on inactivation of PERK/ATF4 pathway.

Conclusion

To conclude, downregulation of NOX4 could exert ovary-protecting effects in DHEA-induced PCOS cellular model through repressing ERS via inactivating PERK/ATF4 pathway.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.