open access
Ca2+ channel subunit a 1D inhibits endometriosis cell apoptosis and mediated by prostaglandin E2
- The Reproductive Medicine Special Hospital of the 1st hospital of Lanzhou University,Lanzhou,Gansu Province, No.1 Donggang road,chengguan distrct,lanzhou city,Gansu province, 730000 lanzhou, China
- Department of Obstetrics and Gynecology, Zhang ye Maternal And Child Health Care Hospital, China, China
open access
Abstract
Objectives: Endometriosis is considered as a chronic pelvic inflammatory disease and prostaglandin E2(PGE2) (a kind of the inflammatory cytokines) was increased in the endometriosis patient’s peritoneal fluid . Ca2+ signal and Ca2+ channels play an important role in cell apoptosis. This study was to explore the L-type calcium channel (Cav1.3) expression and its biological function in endometriosis. Furthermore the molecular mechanism between Cav1.3 and PGE2 was also clarified. Material and methods: The real-time PCR and immunohistochemical were used to detect the expression of Cav1.3. Apoptosis was detected by Flow cytometry assay and Western blot assay. Results: Cav1.3 was high expression in endometriosis tissue and primary endometrial stromal cells (hEM15A). Treatment with PGE2 rapidly inhibited apoptosis and increased Cav1.3 expression in hEM15A . The silencing of Cav1.3 promoted apoptosis, which was unchanged after PGE2 treatment. Moreover, the inhibition of Cav1.3 by shRNA transfection activated cleaved PARP and cleaved caspase-3. Conclusions: These available evidences suggest that Cav1.3 is required for PGE2 induction apoptosis and relates to the pathophysiology of endometriosis. Interference with Cav1.3 may offer a neo-therapeutic window in endometriosis treatment.
Abstract
Objectives: Endometriosis is considered as a chronic pelvic inflammatory disease and prostaglandin E2(PGE2) (a kind of the inflammatory cytokines) was increased in the endometriosis patient’s peritoneal fluid . Ca2+ signal and Ca2+ channels play an important role in cell apoptosis. This study was to explore the L-type calcium channel (Cav1.3) expression and its biological function in endometriosis. Furthermore the molecular mechanism between Cav1.3 and PGE2 was also clarified. Material and methods: The real-time PCR and immunohistochemical were used to detect the expression of Cav1.3. Apoptosis was detected by Flow cytometry assay and Western blot assay. Results: Cav1.3 was high expression in endometriosis tissue and primary endometrial stromal cells (hEM15A). Treatment with PGE2 rapidly inhibited apoptosis and increased Cav1.3 expression in hEM15A . The silencing of Cav1.3 promoted apoptosis, which was unchanged after PGE2 treatment. Moreover, the inhibition of Cav1.3 by shRNA transfection activated cleaved PARP and cleaved caspase-3. Conclusions: These available evidences suggest that Cav1.3 is required for PGE2 induction apoptosis and relates to the pathophysiology of endometriosis. Interference with Cav1.3 may offer a neo-therapeutic window in endometriosis treatment.
Keywords
endometriosis; Cav1.3; apoptosis; PGE2
Title
Ca2+ channel subunit a 1D inhibits endometriosis cell apoptosis and mediated by prostaglandin E2
Journal
Issue
Article type
Research paper
Pages
669-674
Published online
2019-12-31
Page views
1922
Article views/downloads
1287
DOI
Pubmed
Bibliographic record
Ginekol Pol 2019;90(12):669-674.
Keywords
endometriosis
Cav1.3
apoptosis
PGE2
Authors
Yuan Yang
Yue Yuan
Xiaoling Ma
Fuling Xing
- Klemmt PAB, Starzinski-Powitz A. Molecular and Cellular Pathogenesis of Endometriosis. Curr Womens Health Rev. 2018; 14(2): 106–116.
- Prescott J, Farland LV, Tobias DK, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod. 2016; 31(7): 1475–1482.
- Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand. 2017; 96(6): 659–667.
- Hurt KJ. Pocket Obstetrics and Gynecology. Wolters Kluwer Health, Philadelphia, PA 2015.
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646–674.
- Vanaja SK, Rathinam VAK, Fitzgerald KA. Mechanisms of inflammasome activation: recent advances and novel insights. Trends Cell Biol. 2015; 25(5): 308–315.
- Chuang PC, Lin YJ, Wu MH, et al. Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis. Am J Pathol. 2010; 176(2): 850–860.
- Banu SK, Lee J, Speights VO, et al. Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms. Mol Endocrinol. 2009; 23(8): 1291–1305.
- Hsu CC, Lu CW, Huang BM, et al. Cyclic adenosine 3',5'-monophosphate response element-binding protein and CCAAT/enhancer-binding protein mediate prostaglandin E2-induced steroidogenic acute regulatory protein expression in endometriotic stromal cells. Am J Pathol. 2008; 173(2): 433–441.
- Bulayeva NN, Wozniak AL, Lash LL, et al. Mechanisms of membrane estrogen receptor-alpha-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line. Am J Physiol Endocrinol Metab. 2005; 288(2): E388–E397.
- Chen R, Zeng X, Zhang R, et al. Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers. Urol Oncol. 2014; 32(5): 524–536.
- Hao J, Bao X, Jin Bo, et al. Ca2+ channel subunit α 1D promotes proliferation and migration of endometrial cancer cells mediated by 17β-estradiol via the G protein-coupled estrogen receptor. FASEB J. 2015; 29(7): 2883–2893.
- Ji Y, Han Z, Shao L, et al. Ultrasound-targeted microbubble destruction of calcium channel subunit α 1D siRNA inhibits breast cancer via G protein-coupled receptor 30. Oncol Rep. 2016; 36(4): 1886–1892.
- Guzman JN, Ilijic E, Yang B, et al. Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress. J Clin Invest. 2018; 128(6): 2266–2280.
- Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997; 67(5): 817–821.
- Cho S, Mutlu L, Zhou Y, et al. Aromatase inhibitor regulates let-7 expression and let-7f-induced cell migration in endometrial cells from women with endometriosis. Fertil Steril. 2016; 106(3): 673–680.
- Sun Y, Guo W, Ren T, et al. Gli1 inhibition suppressed cell growth and cell cycle progression and induced apoptosis as well as autophagy depending on ERK1/2 activity in human chondrosarcoma cells. Cell Death Dis. 2014; 5: e979.
- Yang Y, Zhou J, Li X, et al. Gefitinib enhances sensitivity of endometrial cancer cells to progestin therapy via dual-specificity phosphatase 1. Oncotarget. 2017; 8(70): 115360–115369.
- Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972; 26(4): 239–257.
- Gruber HE, Hoelscher GL, Bethea S, et al. Mitochondrial Membrane Potential and Nuclear and Gene Expression Changes During Human Disc Cell Apoptosis: In Vitro and In Vivo Annulus Findings. Spine (Phila Pa 1976). 2015; 40(12): 876–882.
- Xu P, Cai X, Zhang W, et al. Flavonoids of Rosa roxburghii Tratt exhibit radioprotection and anti-apoptosis properties via the Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway. Apoptosis. 2016; 21(10): 1125–1143.