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  • In PMCA Mg favors the conversion E

    2024-06-07

    In PMCA, Mg2+ favors the conversion E1P → E2P [13] and, as in SERCA [11], it accelerates the phosphorylation displacing the E1–E2 equilibrium towards E1. In SERCA, Sørensen et al. [41], proposed that ATP reacts by an associative mechanism mediated by two Mg2+ ions to form an aspartyl-phosphorylated intermediate state (E1~P). Cornelius et al. [42] suggested that Al3+ can replace Mg2+ in its specific site in Na+/K+-ATPase. Our results show that Al3+ inhibits PMCA activity by stabilizing a phosphorylated intermediate, suggesting that it could replace Mg2+ and prevent the dephosphorylation of the enzyme. The possibility that Al3+ could inhibit through the binding to ATP can be ruled out by the experiments in this paper (see Fig. 6). In PMCA, LaIII replaces Mg2+ preventing the E1P → E2P isomerization step thus increasing both the PMCA EP level [14,15] and the Ca2+ occlusion [43]. According to the fact that LaIII stabilizes the E1P conformation, EPLa is quickly dephosphorylated in the presence of ADP with a monoexponential behaviour [15], The time courses of EPAl dephosphorylation in the presence of ADP or ATP show a biphasic behaviour indicating that this complex is composed by both E2P and E1P. However, unlike for LaIII, 65% of EPAl is in the E2P conformation.
    Conclusion In short, we show that aluminum inhibits SERCA by a slowly reversible mechanism in which Al3+ displaces Ca2+ from its binding site. Conversely, in PMCA Al3+ inhibits the dephosphorylation step fixing the pump in a very stable complex composed mainly by the conformer E2P.
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    Introduction
    Menopause is a state when changes in the pH of vaginal fluid become apparent, whereby pH increases (Panda et al. 2014). The increased in fluid pH (>4.5) predisposes vagina to infection. Besides, during menopause, low Kaempferol levels can cause the glycogen content in the vagina to decrease and this results in lesser production of lactic acid by vaginal flora i.e Lactobacillus sp, ultimately causing vaginal fluid pH to increase (Mirmonsef et al. 2014). The pH of vaginal fluid depends upon balance between H+ and HCO3− (Frobenius and Bogdan, 2015, Shen et al., 2016). H+ secretion via V-ATPase, a multi-subunit protein which utilizes energy from ATP to transport H+ across the cell into the lumen could contribute to pH decrease (Karim et al., 2016a, Karim et al., 2016b). Besides, increased H+ generation involving carbonic anhydrase (CA) (Karim et al. 2016a) which exists in several isoforms including membrane-bound CAIV, CAIX, and CAXII and cytosolic CAI, CAII, CAIII, CAVII, and CAXIII could also lead to pH decrease. The membrane-bound and cytosolic CA have been reported to be expressed in the female reproductive tract (Hynninen et al. 2004). Marantodes pumilum is a herb popularly used by the women in Southeast to involute the uterus post-delivery. Besides, it is also used to facilitate childbirth, treat irregular menstrual cycle and painful menses as well as help to promote sexual well-being of women (Chua et al. 2012). In Malaysia, this herb is known as Kacip Fatimah. All parts of the plant are consumed mainly in the form of decoction drink and studies have found that M. pumilum leaves contains phenols, flavonoids and saponins (Karimi and Jaafar 2011;Karimi et al. 2016). In view of the reported pharmacological effects of this plant on the female reproductive system and the possibility that it might contain compounds that have estrogen-like activities, this study hypothesized that the leaves of M. pumilum could be used to ameliorate the increase in vaginal fluid pH due to estrogen deficiency. Therefore, this study aims to investigate changes in the vaginal fluid pH and the mechanisms underlying the pH changes such as changes in expression of V-ATPase and CA in the vagina of sex-steroid deficient animal model representing menopause.
    Materials and methods