PMID- 15781737
OWN - NLM
STAT- MEDLINE
DCOM- 20051027
LR  - 20091119
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 111
IP  - 12
DP  - 2005 Mar 29
TI  - Adenovirus-mediated overexpression of diacylglycerol kinase-zeta inhibits 
      endothelin-1-induced cardiomyocyte hypertrophy.
PG  - 1510-6
AB  - BACKGROUND: Diacylglycerol (DAG) is a lipid second messenger that transiently 
      accumulates in cells stimulated by endothelin-1 (ET-1) and other Galphaq 
      protein-coupled receptor agonists. Diacylglycerol kinase (DGK) is thought to be 
      an enzyme that controls the cellular levels of DAG by converting it to 
      phosphatidic acid; however, the functional role of DGK has not been examined in 
      cardiomyocytes. Because DGK inactivates DAG, a strong activator of protein kinase 
      C (PKC), we hypothesized that DGK inhibited ET-1-induced activation of a DAG-PKC 
      signaling cascade and subsequent cardiomyocyte hypertrophy. METHODS AND RESULTS: 
      Real-time reverse transcription-polymerase chain reaction demonstrated a 
      significant increase of DGK-zeta mRNA by ET-1 in cardiomyocytes. To determine the 
      functional role of DGK-zeta, we overexpressed DGK-zeta in cardiomyocytes using a 
      recombinant adenovirus encoding rat DGK-zeta (Ad-DGKzeta). ET-1-induced 
      translocation of PKC-epsilon was blocked by Ad-DGKzeta (P<0.01). Ad-DGKzeta also 
      inhibited ET-1-induced activation of extracellular signal-regulated kinase 
      (P<0.01). Luciferase reporter assay revealed that ET-1-mediated increase of 
      activator protein-1 (AP1) DNA-binding activity was significantly inhibited by 
      DGK-zeta (P<0.01). In cardiomyocytes transfected with DGK-zeta, ET-1 failed to 
      cause gene induction of atrial natriuretic factor, increases in [3H]-leucine 
      uptake, and increases in cardiomyocyte surface area. CONCLUSIONS: We demonstrated 
      for the first time that DGK-zeta blocked ET-1-induced activation of the 
      PKC-epsilon-ERK-AP1 signaling pathway, atrial natriuretic factor gene induction, 
      and resultant cardiomyocyte hypertrophy. DGK-zeta might act as a negative 
      regulator of hypertrophic program in response to ET-1, possibly by controlling 
      cellular DAG levels.
FAU - Takahashi, Hiroki
AU  - Takahashi H
AD  - First Department of Internal Medicine, Yamagata University School of Medicine, 
      Yamagata, Japan.
FAU - Takeishi, Yasuchika
AU  - Takeishi Y
FAU - Seidler, Tim
AU  - Seidler T
FAU - Arimoto, Takanori
AU  - Arimoto T
FAU - Akiyama, Hideyuki
AU  - Akiyama H
FAU - Hozumi, Yasukazu
AU  - Hozumi Y
FAU - Koyama, Yo
AU  - Koyama Y
FAU - Shishido, Tetsuro
AU  - Shishido T
FAU - Tsunoda, Yuichi
AU  - Tsunoda Y
FAU - Niizeki, Takeshi
AU  - Niizeki T
FAU - Nozaki, Naoki
AU  - Nozaki N
FAU - Abe, Jun-ichi
AU  - Abe J
FAU - Hasenfuss, Gerd
AU  - Hasenfuss G
FAU - Goto, Kaoru
AU  - Goto K
FAU - Kubota, Isao
AU  - Kubota I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050321
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Diglycerides)
RN  - 0 (Endothelin-1)
RN  - 0 (RNA, Messenger)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - EC 2.7.1.- (Prkce protein, rat)
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-epsilon)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Atrial Natriuretic Factor/genetics
MH  - Cell Enlargement/*drug effects
MH  - Cells, Cultured
MH  - Diacylglycerol Kinase/genetics/*physiology
MH  - Diglycerides/metabolism
MH  - Endothelin-1/antagonists & inhibitors/*pharmacology
MH  - Gene Expression Regulation
MH  - Hypertrophy/*etiology/pathology
MH  - Myocytes, Cardiac/metabolism/*pathology
MH  - Protein Kinase C/metabolism
MH  - Protein Kinase C-epsilon
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Second Messenger Systems
MH  - Transcriptional Activation
MH  - Transduction, Genetic
EDAT- 2005/03/23 09:00
MHDA- 2005/10/28 09:00
CRDT- 2005/03/23 09:00
PHST- 2005/03/23 09:00 [pubmed]
PHST- 2005/10/28 09:00 [medline]
PHST- 2005/03/23 09:00 [entrez]
AID - 01.CIR.0000159339.00703.22 [pii]
AID - 10.1161/01.CIR.0000159339.00703.22 [doi]
PST - ppublish
SO  - Circulation. 2005 Mar 29;111(12):1510-6. doi: 10.1161/01.CIR.0000159339.00703.22. 
      Epub 2005 Mar 21.