2. Academic Validation
  3. Protegrin-1 inhibits porcine ovarian granulosa cell apoptosis from H2O2-induced oxidative stress via the PERK/eIF2α/CHOP signaling pathway in vitro

Protegrin-1 inhibits porcine ovarian granulosa cell apoptosis from H2O2-induced oxidative stress via the PERK/eIF2α/CHOP signaling pathway in vitro

  • Theriogenology. 2022 Feb:179:117-127. doi: 10.1016/j.theriogenology.2021.11.022.
Xuan Li 1,  Yufeng Lin 1,  Jiawei Yao 1,  Bo Pan 2,  Xiaoshu Zhan 3,  Zhisheng Chen 1,  Yinshan Bai 1,  Hui Zhang 1,  Bingyun Wang 1,  Shengfeng Chen 1,  Julang Li 2,  Canying Liu 4
Affiliations

Affiliations

  • 1 Department of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528000, China.
  • 2 Department of Animal and Poultry Science, University of Guelph, Guelph, ON, N1G 2W1, Canada.
  • 3 Department of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528000, China; Department of Animal and Poultry Science, University of Guelph, Guelph, ON, N1G 2W1, Canada.
  • 4 Department of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528000, China. Electronic address: liucy3032@163.com.
PMID: 34864562 DOI: 10.1016/j.theriogenology.2021.11.022
Abstract

In mammals, oxidative stress-induced Apoptosis of granulosa cells is one of the major causes of follicular atresia, affecting ovarian physiological function. Protegrin-1 (PG-1) is an antimicrobial peptide with effective antimicrobial activity, immunomodulatory function, and porcine growth-promoting effects. PG-1 has been detected in porcine ovaries follicles. This study aimed to investigate the effect of PG-1 on oxidative stress-induced Apoptosis of porcine ovarian granulosa cells and the underlying molecular mechanism. Granulosa cells were obtained from porcine follicles and treated with H2O2 to establish the oxidative stress model, and then treated with or without PG-1 (10 μg/mL). PG-1 significantly suppressed H2O2-induced Apoptosis in granulosa cells after 24 h of treatment. Furthermore, these results revealed that PG-1 increased the mRNA and protein expression of anti-apoptotic B cell lymphoma/leukemia 2 (BCL2) and the BCL2/Bcl-2-associated X protein (Bax) ratio while decreasing the expression of pro-apoptotic Bax and active Caspase-3. Using Western blot analysis, it was found that PG-1 decreased the phosphorylation of RNA-like endoplasmic reticulum kinase (PERK) and the α-subunit of eukaryotic initiation factor 2 (eIF2α) as well as the protein expression level of CCAAT enhancer-binding protein homologous protein (CHOP), all of which were increased by H2O2. Moreover, inhibitors against PERK and phospho-eIF2ɑ both suppressed the H2O2-induced granulosa cells Apoptosis and enhanced the anti-apoptosis effect of PG-1. Taken together, our findings demonstrated that PG-1 inhibited porcine ovarian granulosa cell Apoptosis from oxidative stress via the PERK/eIF2α/CHOP signaling pathway in vitro, which suggests the novel regulatory function of the antimicrobial peptide in the ovary.

Keywords

Apoptosis; Oxidative stress; PERK/eIF2α/CHOP signaling pathway; Porcine ovarian granulosa cell; Protegrin-1.

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