自噬
细胞凋亡
细胞生物学
信号转导
激活剂(遗传学)
化学
生物
基因
生物化学
作者
Xin Zhang,Ming Li,Mengyi Huang,Hao Peng,Xiaoming Song,Lei Chen,Wen Yang Hu,Wenhao Xu,Rongrong Luo,Dongyang Han,Yan Shi,Yajie Cao,Xun Li,Chuanhuo Hu
标识
DOI:10.1016/j.theriogenology.2021.12.024
摘要
RFamide-related peptide-3 (RFRP-3) has been proposed as a key inhibitory regulator of mammalian reproduction. Our previous studies demonstrated that RFRP-3 mediated apoptosis and autophagy of the epididymis in rats and inhibited porcine granulosa cell (GC) proliferation. However, the molecular mechanisms of the RFRP-3 effect on porcine GC apoptosis and autophagy have not been studied before. Herein, we first investigated the role of RFRP-3 in apoptosis and autophagy in cultured porcine GCs in vitro. Our results showed that different doses of RFRP-3 dose-dependently elevated the expression of autophagy markers at both the mRNA and protein levels, whereas the expression of apoptosis markers exhibited a bidirectional, dose-dependent effect. Because the p38MAPK signaling pathway plays essential roles in apoptosis and autophagy, we subsequently evaluated the effect of RFRP-3 on p38MAPK activation. The results showed that 10-6 M RFRP-3 treatment not only significantly decreased p38MAPK phosphorylation but also inhibited the p38MAPK activator U-46619 to promote p38MAPK activation in porcine GCs. Finally, we applied U-46619 to investigate the role of the p38MAPK signaling pathway in apoptosis and autophagy in RFRP-3-treated porcine GCs. The results showed that all doses of RFRP-3 significantly inhibited the U-46619-induced increase in apoptosis in a dose-dependent manner. However, except for the U-46619-induced Beclin-1 expression increase, which was significantly suppressed in high-dose RFRP-3-treated porcine GCs, other doses of RFRP-3 treatment strengthened the U-46619-induced increase in other autophagy markers. In summary, our data demonstrate a critical role for the p38MAPK signaling pathway in the porcine GC cellular response to RFRP-3 by controlling the balance between apoptosis and autophagy.
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