Evidence for a role of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in thapsigargin and Bcl-2 induced changes in Xenopus laevis oocyte maturation

Abstract

Thapsigargin (Tg), a selective inhibitor of sarcoplasmic/ endoplasmic reticulum Ca 2+ -ATPase (SERCA), causes depletion of intracellular Ca 2+ stores, hence activation of capacitative Ca 2+ entry (CCE). Incubation of Xenopus laevis oocytes with Tg resulted in an increased rate of progesterone-induced meiotic maturation. Non-mitochondrial 45 Ca 2+ uptake by SERCA-containing microsomes prepared from control wild-type oocytes microinjected with sterile water was inhibited essentially 100% by Tg. However, overexpression of Bcl-2, an oncogene known to protect against Tg-induced apoptosis in certain cell types, resulted in only 40% inhibition of microsomal 45 Ca 2+ uptake by Tg while non-inhibited 45 Ca 2+ uptake remained unchanged. Moreover Bcl-2 overexpression also protected against inhibition of CCE. I Cl(Ca) was similar in Bcl-2-overexpressing and control oocytes when intracellular Ca 2+ store depletion was induced by microinjection of inositol 1,4,5-trisphosphate (InsP 3 ) and other means and when CCE was induced by means independent of SERCA inhibition. Our data indicate that Bcl-2 a ects neither the InsP 3 receptor nor Ca 2+ entry itself. At the end of a 24-h period after progesterone addition to the medium, only 25% of Bcl-2-overexpressing oocytes had matured compared to 85% of control oocytes. Our data suggest that SERCA participates in Xenopus oocyte maturation by controlling cytosolic Ca 2+ and/or intracellular Ca 2+ stores, hence CCE. An observed progesterone-dependent protein kinase-catalysed phosphorylation of SERCA is further indication of its role in oocyte maturation. Oncogene (2001) 20, 933 ± 941.

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

“…While previous reports have demonstrated that BCL-2 can have both positive and negative effects on SERCA structure and function [16,43,44], to our knowledge the data in Figure 2 are the first to indicate that BCL-2 may act to stabilize SERCA3 levels in primary human AML cells. Previous studies indicate that the BH4 domain is mainly responsible for the role of BCL-2 in regulating ER and mitochondrial calcium [17,[45][46][47]. As venetoclax was designed as a BH3 mimetic, it was not expected to influence calcium levels.…”

Subcellular localization of calcium and Ca-ATPase activity during nuclear maturation inBufo arenarumoocytes

“…As the maturation process progressed (4–5 h after progesterone treatment), the Ca 2+ deposits could be observed on the surface of the oocyte cortex. At this level, the presence of the calcium inside the vesicles originated either by the disruption of AL or from the ER together with the detection of Ca-ATPase at the membrane of these structures suggests the participation of this enzyme in the maturation process by controlling cytosolic calcium and/or intracellular Ca 2+ stores (Kobrinsky & Kirchberger, 2001).…”