PMID- 19244478
OWN - NLM
STAT- MEDLINE
DCOM- 20090625
LR  - 20211020
IS  - 0363-6143 (Print)
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 296
IP  - 5
DP  - 2009 May
TI  - Effects of thapsigargin and phenylephrine on calcineurin and protein kinase C 
      signaling functions in cardiac myocytes.
PG  - C992-C1002
LID - 10.1152/ajpcell.00594.2008 [doi]
AB  - Neonatal rat cardiac myocytes were exposed to 10 nM thapsigargin (TG) or 20 muM 
      phenylephrine (PE) to compare resulting alterations of Ca(2+) homeostasis. Either 
      treatment results in resting cytosolic [Ca(2+)] rise and reduction of Ca(2+) 
      signals in myocytes following electrical stimuli. In fact, ATP-dependent Ca(2+) 
      transport is reduced due to catalytic inhibition of sarcoplasmic reticulum ATPase 
      (SERCA2) by TG or reduction of SERCA2 protein expression by PE. A marked rise of 
      nuclear factor of activated T cells (NFAT)-dependent expression of transfected 
      luciferase cDNA is produced by TG or PE, which is dependent on increased NFAT 
      dephosphorylation by activated calcineurin and reduced phosphorylation by 
      inactivated glycogen synthase kinase 3beta. Expression of SERCA2 (inactivated) 
      protein is increased following exposure to TG, whereas no hypertrophy is 
      produced. On the contrary, SERCA2 expression is reduced, despite high CN 
      activity, following protein kinase C (PKC) activation by PE (or phorbol 
      12-myristate 13-acetate) under conditions producing myocyte hypertrophy. Both 
      effects of TG and PE are dependent on NFAT dephosphorylation by CN, as 
      demonstrated by CN inhibition with cyclosporine (CsA). However, the hypertrophy 
      program triggered by PKC activation bypasses SERCA2 transcription and expression 
      due to competitive recruitment of NFAT and/or other transcriptional factors. A 
      similar dependence on CN activation, but relative reduction under conditions of 
      PKC activation, involves transcription and expression of the Na(+)/Ca(2+) 
      exchanger-1. On the other hand, significant upregulation of transient receptor 
      potential channel proteins is noted following PKC activation. The observed 
      alterations of Ca(2+) homeostasis may contribute to development of contractile 
      failure.
FAU - Prasad, Anand Mohan
AU  - Prasad AM
AD  - California Pacific Medical Center Research Institute, San Francisco, CA 94107, 
      USA.
FAU - Inesi, Giuseppe
AU  - Inesi G
LA  - eng
GR  - R01 HL-69830/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090225
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Atp2a2 protein, rat)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (sodium-calcium exchanger 1)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
RN  - 1WS297W6MV (Phenylephrine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.3.16 (Calcineurin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Calcineurin/*metabolism
MH  - Calcium Signaling/physiology
MH  - Cardiomegaly/metabolism
MH  - Cardiotonic Agents/pharmacology
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Cytosol/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression/drug effects
MH  - Myocytes, Cardiac/cytology/*drug effects/*metabolism
MH  - NFATC Transcription Factors/metabolism
MH  - Phenylephrine/*pharmacology
MH  - Protein Kinase C/*metabolism
MH  - Rats
MH  - Sarcoplasmic Reticulum/drug effects/enzymology
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics/metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Sodium-Calcium Exchanger/metabolism
MH  - TRPC Cation Channels/metabolism
MH  - Thapsigargin/*pharmacology
PMC - PMC2681384
EDAT- 2009/02/27 09:00
MHDA- 2009/06/26 09:00
PMCR- 2010/05/01
CRDT- 2009/02/27 09:00
PHST- 2009/02/27 09:00 [entrez]
PHST- 2009/02/27 09:00 [pubmed]
PHST- 2009/06/26 09:00 [medline]
PHST- 2010/05/01 00:00 [pmc-release]
AID - 00594.2008 [pii]
AID - C-00594-2008 [pii]
AID - 10.1152/ajpcell.00594.2008 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 May;296(5):C992-C1002. doi: 
      10.1152/ajpcell.00594.2008. Epub 2009 Feb 25.