PMID- 8389460 OWN - NLM STAT- MEDLINE DCOM- 19930707 LR - 20191210 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 90 IP - 11 DP - 1993 Jun 1 TI - Intracellular Ca2+ pool content is linked to control of cell growth. PG - 4986-90 AB - A close correlation was observed between intracellular Ca2+ pool depletion and refilling and the onset of DNA synthesis and proliferation of DDT1MF-2 smooth muscle cells. The intracellular Ca2+ pump inhibitors 2,5-di-tert-butyl-hydroquinone (DBHQ) and thapsigargin (TG) specifically 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 following release of DBHQ-arrested cells. The precise relationship between Ca2+ pump blockade and growth arrest indicates that Ca2+ pool emptying maintains cells in a G0-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 G0 to G1 transition depends upon signals generated from the InsP3-sensitive Ca2+ pool. FAU - Short, A D AU - Short AD AD - Department of Biological Chemistry, University of Maryland School of Medicine, Baltimore 21201. FAU - Bian, J AU - Bian J FAU - Ghosh, T K AU - Ghosh TK FAU - Waldron, R T AU - Waldron RT FAU - Rybak, S L AU - Rybak SL FAU - Gill, D L AU - Gill DL LA - eng GR - NS19304/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antioxidants) RN - 0 (Hydroquinones) RN - 0 (Terpenes) RN - 56092-81-0 (Ionomycin) RN - 67526-95-8 (Thapsigargin) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - C12674942B (2-tert-butylhydroquinone) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) RN - TSN3DL106G (Fura-2) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Calcium/*metabolism MH - Calcium-Transporting ATPases/antagonists & inhibitors/drug effects/*physiology MH - Cell Division/drug effects/*physiology MH - Cell Line MH - Fura-2 MH - Hydroquinones/pharmacology MH - Inositol 1,4,5-Trisphosphate/metabolism MH - Ionomycin/pharmacology MH - Kinetics MH - Muscle, Smooth MH - Spectrometry, Fluorescence MH - Terpenes/pharmacology MH - Thapsigargin MH - Time Factors PMC - PMC46638 EDAT- 1993/06/01 00:00 MHDA- 1993/06/01 00:01 PMCR- 1993/12/01 CRDT- 1993/06/01 00:00 PHST- 1993/06/01 00:00 [pubmed] PHST- 1993/06/01 00:01 [medline] PHST- 1993/06/01 00:00 [entrez] PHST- 1993/12/01 00:00 [pmc-release] AID - 10.1073/pnas.90.11.4986 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4986-90. doi: 10.1073/pnas.90.11.4986.