Ca2+ channel subunit a 1D inhibits endometriosis cell apoptosis and mediated by prostaglandin E2

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.

Molecular and Clinical Insights on the Complex Interaction between Oxidative Stress, Apoptosis, and Endobiota in the Pathogenesis of Endometriosis

“…The much more complex TNF-α-mediated apoptosis in EMS still remains to be fully elucidated, since Tian et al and Long et al [50,51] described the mechanism through which the activation of this process could also be mediated by death-associated protein kinase 1 (DAPK1), c-Jun, and miRNAs. Another yet fully undiscovered mechanism is the implication of Ca+ and Cav1.3 channels in cell proliferation, aggregation, and apoptosis [52]. However, Yang et al [52] already described the implication of the Cav1.3 channel, which is expressed in EMS tissue and primary ESCs cells and is highly sensitive to prostaglandin 2 and could modulate caspase 3-mediated apoptosis.…”

“…Another yet fully undiscovered mechanism is the implication of Ca+ and Cav1.3 channels in cell proliferation, aggregation, and apoptosis [52]. However, Yang et al [52] already described the implication of the Cav1.3 channel, which is expressed in EMS tissue and primary ESCs cells and is highly sensitive to prostaglandin 2 and could modulate caspase 3-mediated apoptosis. The mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway has also been proposed to fulfil the important role(s) in cell proliferation, apoptosis, and migration.…”

Effects of polyamine synthesis enzymes on angiogenesis and apoptosis during endometriosis

“…Endometriosis is a common gynecological disease of benign, hormonal origin. Pelvic pain, dysmenorrhea, dyspareunia, and infertility are common clinical findings of endometriosis [14]. Histologically, it is accepted that benign endometriotic lesions occur as a result of genetic errors that can also lead to malignant transformations.…”

Plasma and Peritoneal Poly (ADP-Ribose) Polymerase Levels in Patients with Endometriosis

“…What is more, PARP-1 expression was reduced in the subgroup of women with endometriosis and cabergoline intake. In a study by Yang et al the authors propose a novel possible mechanism of endometriosis pathophysiology involving PGE2-induced apoptosis suppression by upregulation of Cav1.3 expression resulting in decreased cleaved PARP and caspase 3 levels [ 46 ].…”