PMID- 8746951
OWN - NLM
STAT- MEDLINE
DCOM- 19961008
LR  - 20191210
IS  - 0143-4160 (Print)
IS  - 0143-4160 (Linking)
VI  - 18
IP  - 6
DP  - 1995 Dec
TI  - Protein kinase C modulates cytosolic free calcium by stimulating calcium pump 
      activity in Jurkat T cells.
PG  - 526-41
AB  - Although protein kinase C (PKC) activation has been shown to inhibit Ca2+ influx 
      in T lymphocytes, the role of PKC on Ca2+ sequestration or extrusion processes 
      has not been fully explored. We examined the effect of CD3 stimulation and PKC 
      activators on cytosolic Ca2+ (Ca2+i) extrusion and 45Ca2+ efflux in human 
      leukemic Jurkat T cells. Treatment of Fura-2 loaded cells with phorbol 
      12-myristate 13-acetate (PMA) or thymeleatoxin (THYM) resulted in a decrease in 
      Ca2+i both in the presence and absence of extracellular Ca2+, whereas inactive 
      phorbol esters had no effect. PKC activators added at the peak of a Ca2+i 
      transient induced by anti-CD3 mAb, ionomycin or thapsigargin (TG) stimulated the 
      rate and extent of return of Ca2+i to basal levels by 17-53%. PKC stimulation of 
      the Ca2+i decline was not enhanced by the presence of Na+, indicating that PKC 
      activators increase Ca2+ pump activity rather than a Na+/Ca2+ exchange mechanism. 
      As CD3 receptor activation enhanced the Ca2+i decline in TG-treated cells, 
      antigen-mediated activation of phospholipase C (PLC) signaling includes enhanced 
      Ca2+ extrusion at the plasma membrane. The effect of PKC activators on parameters 
      of Ca2+i extrusion were further explored. PMA significantly increased the rate of 
      Ca2+ extrusion in TG-treated cells from 0.28 +/- 0.02 to 0.35 +/- 0.03 s-1 (mean 
      +/- SEM) and stimulated the initial rate of 45Ca2+ efflux by 69% compared to 
      inactive phorbol ester treated cells. The effects of PKC activation on the Ca2+i 
      decline were eliminated by PKC inhibitors, PKC down regulation (24 h PMA 
      pretreatment), ATP-depletion and conditions that inhibited the Ca2+ pump. In 
      contrast, pretreatment of cells with okadaic acid enhanced the PMA-stimulated 
      response. We suggest that Jurkat T cells contain a PKC-sensitive Ca2+ extrusion 
      mechanism likely to be the Ca2+ pump. In lymphocytes, receptor/PLC-linked PKC 
      activation modulates Ca2+i not only by inhibiting Ca2+ influx but also by 
      stimulating plasma membrane Ca2+i extrusion.
FAU - Balasubramanyam, M
AU  - Balasubramanyam M
AD  - Hypertension Research Center, University of Medicine and Dentistry of New Jersey, 
      New Jersey Medical School, Newark, USA.
FAU - Gardner, J P
AU  - Gardner JP
LA  - eng
GR  - HL-44196/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (Alkaloids)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Ionophores)
RN  - 0 (Naphthalenes)
RN  - 0 (Phorbol Esters)
RN  - 0 (Terpenes)
RN  - 56092-81-0 (Ionomycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 6I3K30563S (Lanthanum)
RN  - 94482-56-1 (thymeleatoxin)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - H88EPA0A3N (Staurosporine)
RN  - I271P23G24 (calphostin C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SY7Q814VUP (Calcium)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - Alkaloids/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors/*metabolism
MH  - Cytosol/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Fluorescent Dyes
MH  - Fura-2
MH  - Humans
MH  - Ionomycin/pharmacology
MH  - Ionophores/pharmacology
MH  - Lanthanum/pharmacology
MH  - Leukemia
MH  - Naphthalenes/pharmacology
MH  - Phorbol Esters/pharmacology
MH  - Protein Kinase C/*metabolism
MH  - Sodium/pharmacology
MH  - Staurosporine
MH  - T-Lymphocytes/cytology/drug effects/enzymology
MH  - Terpenes/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thapsigargin
MH  - Tumor Cells, Cultured/drug effects/enzymology
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
AID - 0143-4160(95)90015-2 [pii]
AID - 10.1016/0143-4160(95)90015-2 [doi]
PST - ppublish
SO  - Cell Calcium. 1995 Dec;18(6):526-41. doi: 10.1016/0143-4160(95)90015-2.