Oxidized high-density lipoprotein promotes rat ovarian granulosa cell apoptosis through reactive oxygen species-initiated p38 signaling pathway

doi:10.12307/2024.168

Abstract

Abstract: BACKGROUND: Oxidative modification of high-density lipoprotein occurs in patients with polycystic ovary syndrome. However, the relationship between oxidized high-density lipoprotein and ovulation dysfunction and its mechanism are unknown.
OBJECTIVE: To investigate the effect and potential mechanism of oxidized high-density lipoprotein on ovarian granulosa cell apoptosis.
METHODS: Polycystic ovary syndrome rat model was established, then the high-density lipoprotein was harvested from the rat serum of heart blood. The degree of oxidation of the high-density lipoprotein was detected by high-density lipoprotein inflammation index assay, malondialdehyde assay and lipoprotein agarose gel electrophoresis assay. The normal rat ovarian granulosa cells were isolated and treated with high-density lipoprotein and oxidized high-density lipoprotein isolated from the model rat serum. Cell viability was detected by CCK-8 assay. Cell apoptosis was detected by flow cytometry. The generation of reactive oxygen species was detected by H2DCF-DA staining. The p38 signaling activity was detected by western blot assay. Ovarian granulosa cells were pretreated with reactive oxygen species inhibitors N-acetylcysteine, tetramethylpiperidine (Tempol) and p38 inhibitor SB203580, and then treated with oxidized high-density lipoprotein. Finally, cell apoptosis, reactive oxygen species production and p38 signaling activity were detected.
RESULTS AND CONCLUSION: A portion of the high-density lipoprotein from the serum of polycystic ovary syndrome model rats affected oxidative modification. High-density lipoprotein and oxidized high-density lipoprotein isolated from the model rat serum inhibited granulosa cell viability and promoted apoptosis (all P < 0.05). They promoted rat granulosa cell reactive oxygen species production and p38 activation (all P < 0.05). N-acetylcysteine, Tempol and SB203580 reversed oxidized high-density lipoprotein induced granulosa cell apoptosis (all P < 0.05). N-acetylcysteine and Tempol suppressed oxidized high-density lipoprotein-induced p38 activation (all P < 0.05). SB203580 did not have a regulatory effect on reactive oxygen species production (P > 0.05). In summary, polycystic ovary syndrome can promote partial oxidative modification of high-density lipoprotein. The oxidized high-density lipoprotein promotes rat granulosa cell apoptosis by the activation of the reactive oxygen species-initiated p38 signaling pathway.

Key words: polycystic ovary syndrome, oxidized high-density lipoprotein, granulosa cell, apoptosis, reactive oxygen species, p38

CLC Number:

Guo Qin, Wu Minmin, Tao Ying. Oxidized high-density lipoprotein promotes rat ovarian granulosa cell apoptosis through reactive oxygen species-initiated p38 signaling pathway[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(19): 3055-3060.

Figures/Tables 5

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