PMID- 12676772
OWN - NLM
STAT- MEDLINE
DCOM- 20030821
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 285
IP  - 2
DP  - 2003 Aug
TI  - Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide 
      synthase.
PG  - H669-78
AB  - Soluble guanylate cyclase (sGC) is an important downstream intracellular target 
      of nitric oxide (NO) that is produced by endothelial NO synthase (eNOS) and 
      inducible NO synthase (iNOS). In this study, we demonstrate that sGC exists in a 
      complex with eNOS and heat shock protein 90 (HSP90) in aortic endothelial cells. 
      In addition, we show that in aortic smooth muscle cells, sGC forms a complex with 
      HSP90. Formation of the sGC/eNOS/HSP90 complex is increased in response to 
      eNOS-activating agonists in a manner that depends on HSP90 activity. In vitro 
      binding assays with glutathione S-transferase fusion proteins that contain the 
      alpha- or beta-subunit of sGC show that the sGC beta-subunit interacts directly 
      with HSP90 and indirectly with eNOS. Confocal immunofluorescent studies confirm 
      the subcellular colocalization of sGC and HSP90 in both endothelial and smooth 
      muscle cells. Complex formation of sGC with HSP90 facilitates responses to NO 
      donors in cultured cells (cGMP accumulation) as well as in anesthetized rats 
      (hypotension). These complexes likely function to stabilize sGC as well as to 
      provide directed intracellular transfer of NO from NOS to sGC, thus preventing 
      inactivation of NO by superoxide anion and formation of peroxynitrite, which is a 
      toxic molecule that has been implicated in the pathology of several vascular 
      diseases.
FAU - Venema, Richard C
AU  - Venema RC
AD  - Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500, USA.
FAU - Venema, Virginia J
AU  - Venema VJ
FAU - Ju, Hong
AU  - Ju H
FAU - Harris, M Brennan
AU  - Harris MB
FAU - Snead, Connie
AU  - Snead C
FAU - Jilling, Tamas
AU  - Jilling T
FAU - Dimitropoulou, Christiana
AU  - Dimitropoulou C
FAU - Maragoudakis, Michael E
AU  - Maragoudakis ME
FAU - Catravas, John D
AU  - Catravas JD
LA  - eng
GR  - HL 52958/HL/NHLBI NIH HHS/United States
GR  - HL 57201/HL/NHLBI NIH HHS/United States
GR  - HL 62152/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030403
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Benzoquinones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Quinones)
RN  - 169D1260KM (Nitroprusside)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - Z3K3VJ16KU (geldanamycin)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - Benzoquinones
MH  - Cattle
MH  - Cells, Cultured
MH  - Endothelium, Vascular/cytology/*enzymology
MH  - Enzyme Inhibitors/pharmacology
MH  - Guanylate Cyclase/*metabolism
MH  - HSP90 Heat-Shock Proteins/*metabolism
MH  - Lactams, Macrocyclic
MH  - Muscle, Smooth, Vascular/cytology/*enzymology
MH  - Nitric Oxide Donors/pharmacology
MH  - Nitric Oxide Synthase/*metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Nitric Oxide Synthase Type III
MH  - Nitroprusside/pharmacology
MH  - Quinones/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
EDAT- 2003/04/05 05:00
MHDA- 2003/08/22 05:00
CRDT- 2003/04/05 05:00
PHST- 2003/04/05 05:00 [pubmed]
PHST- 2003/08/22 05:00 [medline]
PHST- 2003/04/05 05:00 [entrez]
AID - 01025.2002 [pii]
AID - 10.1152/ajpheart.01025.2002 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H669-78. doi: 
      10.1152/ajpheart.01025.2002. Epub 2003 Apr 3.