| First Author | Hu J | Year | 2020 |
| Journal | Mol Cell Endocrinol | Volume | 511 |
| Pages | 110842 | PubMed ID | 32376276 |
| Mgi Jnum | J:296876 | Mgi Id | MGI:6469198 |
| Doi | 10.1016/j.mce.2020.110842 | Citation | Hu J, et al. (2020) ERO1alpha inhibits cell apoptosis and regulates steroidogenesis in mouse granulosa cells. Mol Cell Endocrinol 511:110842 |
| abstractText | ER oxidoreduclin 1alpha (ERO1alpha), an oxidase that exists in the ER, participates in protein folding and secretion and inhibiting apoptosis, and regulates tumor progression, which is a novel factor of poor cancer prognosis. However, the other physiological functions of ERO1alpha remain undiscovered. Although our preliminary results of this study indicated that ERO1alpha revealed the robust expression in ovary, especially in granulosa cells, the role of ERO1alpha in follicular development is not well known. Therefore, the aims of the present study were to explore the role of ERO1alpha and the possible mechanisms in regulating cell apoptosis and steroidogenesis in ovarian granulosa cells. ERO1alpha was mainly localized in granulosa cells and oocytes in the adult ovary by immunohistochemistry. Western blot analysis showed that the expression of ERO1alpha was highest at oestrous stage during the estrous cycle. The effect of ERO1alpha on cell apoptosis and steroidogenesis was detected by transduction of ERO1alpha overexpression and knockdown lentiviruses into primary cultured granulosa cells. Flow cytometry analysis showed that ERO1alpha decreased granulosa cells apoptosis. Western bolt and RT-qPCR analysis found that ERO1alpha increased the ratio of BCL-2/BAX, and decreased BAD and Caspase-3 expression. ELISA analysis showed that ERO1alpha enhanced estrogen (E2) secretion. Western bolt and RT-qPCR analysis found that ERO1alpha increased StAR, CYP11A1, 3beta-HSD, CYP17A1, and CYP19A1 expression, and decreased CYP1B1 expression. Furthermore, Western bolt analysis found that ERO1alphaincreased PDI and PRDX 4 expression, and activated the PI3K/AKT/mTOR signaling pathway through increasing the phosphorylation of AKT and P70 S6 kinase. In summary, these results suggested that ERO1alpha might play an anti-apoptotic role and regulate steroidogenesis in granulosa cells, at least partly, via activation of the PI3K/AKT/mTOR signaling pathway. |
