Intracellular Ca2+ pool content is linked to control of cell growth.

Abstract

A close correlation was observed between intracellular Ca2+ pool depletion and refiling and the onset of DNA synthesis and proliferation of DDT,MF-2 smooth muscle cells. The intracellular Ca2+ pump inhibitors 2,5-di-tert-butylhydroquinone (DBHQ) and thapsigargin (TG) specificafly emptied identical inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pools and both arrested cell growth at concentrations corresponding to Ca2+ pump blockade. However, an important distinction was observed between the two inhibitors with respect to their reversibility of action. Upon removal of DBHQ from DBHQ-arrested cells, Ca2+ pools immediately refilled, and 14 hr later cells entered S phase followed by normal cell proliferation; the time for entry into S phase was identical to that for cells released from confluence arrest. Although TG irreversibly blocked Ca2+ pumping and emptied Ca2+ pools, high serum treatment of TG-arrested cells induced recovery of functional Ca2+ pools in 6 hr (via probable synthesis of new pump); thereafter cells proceeded to S phase and normal cell proliferation within the same time period (14 hr) as that foUlowing release of DBHQ-arrested cells. The precise relationship between Ca2+ pump blockade and growth arrest indicates that Ca2+ pool emptying maintains cells in a Go-like quiescent state; upon refilling of pools, normal progression into the cell cycle is resumed. It is possible that a specific cell cycle event necessary for Go to G, transition depends upon signals generated from the InsP3-sensitive Ca2+ pool.

Attenuated mesangial cell proliferation related to store-operated Ca2+ entry in aged rat: the role of STIM 1 and Orai 1

“…If the cell is not capable of maintaining an adequate level of Ca 2+ in intracellular stores, many cellular functions including posttranslational modifications of recombinant proteins will be abnormal. Store depletion may elicit problematic protein trafficking, sarcoplasmic reticulum (SR) stress (Cudna and Dickson 2003), growth arrest (Short et al 1993), and apoptosis (He et al 1997) caused by the resulting disturbance of posttranslational protein modification. Ca 2+ influx through SOCE involves keeping a sustained high Ca 2+ concentration in the Ca 2+ stores and refilling the SR when it releases Ca 2+ .…”

Involvement of intact inositol‐1,4,5‐trisphosphate‐sensitive Ca2+ stores in cell cycle progression at the G1/S boundary in serum‐stimulated human fibroblasts

“…In contrast, when thapsigargin was added to actively proliferating cells 24 h after growth stimulation, the growth inhibitory effect of thapsigargin was substantially reduced [8]. These findings led the authors to the conclusion that a specific cell cycle event necessary for the G0/G1 transition depends upon signals generated from functional InsP3-sensitive Ca 2÷ stores [9,10]. However, a question *Corresponding author.…”

“…The increase in [Ca2÷]i is postulated to serve as a mitogenic signalling for re-entry into the cell cycle at the G0/G1 border [6,7]. Recently, Gill and his colleagues [8][9][10] have demonstrated that thapsigargin, which is a selective inhibitor ofendoplasmic reticulum Ca 2+ pump [11] and depletes InsP3-sensitive Ca 2+ stores [12,13], potently inhibits cell proliferation. In their experiments, density-arrested DDT1MF-2 smooth muscle cells were growth-stimulated by trypsinizing and replating into fresh growth media.…”

Expression of a defective mouse mammary tumor virus envelope glycoprotein precursor which binds stably to GRP78 within the lumen of the endoplasmic reticulum is associated with decreased glucocorticoid-induced apoptosis in mouse lymphoma cells

“…A major function of the ER is to sequester and release calcium for use in intracellular signaling (Carafoli, 1987). Moreover, the ER calcium pool is essential for a number of vital cellular functions which include protein processing (Lodish, 1992;Gething, 1992), maintaining high translation rates of newly transcribed messages , preserving the structural integrity of the ER (Koch et al, 1988;Booth and Koch, 1989), and regulating cell proliferation and cell cycle progression (Short et al, 1993). In a previous report, we showed that viral protein-mediated induction of GRP78 synthesis is accompanied by decreased calcium efflux out of the ER lumen following inhibition of ER-associated calciumATPase activity by thapsigargin .…”