PMID- 10559837
OWN - NLM
STAT- MEDLINE
DCOM- 20000201
LR  - 20190516
IS  - 0100-879X (Print)
IS  - 0100-879X (Linking)
VI  - 32
IP  - 11
DP  - 1999 Nov
TI  - Targeting and translocation of endothelial nitric oxide synthase.
PG  - 1361-6
AB  - This review explores advances in our understanding of the intracellular
      regulation of the endothelial isoform of nitric oxide synthase (eNOS) in the
      context of its dynamically regulated subcellular targeting. Nitric oxide (NO) is 
      a labile molecule, and may play important biological roles both within the cell
      in which it is synthesized and in its interactions with nearby cells and
      molecules. The localization of eNOS within the cell importantly influences the
      biological role and chemical fate of the NO produced by the enzyme. eNOS, a
      Ca2+/calmodulin-dependent enzyme, is subject to a complex pattern of
      intracellular regulation, including co- and post-translational modifications and 
      interactions with other proteins and ligands. In endothelial cells and cardiac
      myocytes eNOS is localized in specialized plasmalemmal signal-transducing domains
      termed caveolae; acylation of the enzyme by the fatty acids myristate and
      palmitate is required for targeting of the protein to caveolae. Targeting to
      caveolae facilitates eNOS activation following receptor stimulation. In resting
      cells, eNOS is tonically inhibited by its interactions with caveolin, the
      scaffolding protein in caveolae. However, following agonist activation, eNOS
      dissociates from caveolin, and nearly all the eNOS translocates to structures
      within the cell cytosol; following more protracted incubations with agonists,
      most of the cytosolic enzyme subsequently translocates back to the cell membrane.
      The agonist-induced internalization of eNOS is completely abrogated by chelation 
      of intracellular Ca2+. These rapid receptor-mediated effects are seen not only
      for "classic" eNOS agonists such as bradykinin, but also for estradiol,
      indicating a novel non-genomic role for estrogen in eNOS activation. eNOS
      targeting to the membrane is labile, and is subject to receptor-regulated
      Ca2+-dependent reversible translocation, providing another point for regulation
      of NO-dependent signaling in the vascular endothelium.
FAU - Michel, T
AU  - Michel T
AD  - Brigham and Women's Hospital, West Roxbury VA Medical Center, Harvard Medical
      School, Boston, MA, USA. michel@calvin.bwh.harvard.edu
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Brazil
TA  - Braz J Med Biol Res
JT  - Brazilian journal of medical and biological research = Revista brasileira de
      pesquisas medicas e biologicas
JID - 8112917
RN  - 0 (CAV1 protein, human)
RN  - 0 (Calmodulin)
RN  - 0 (Caveolin 1)
RN  - 0 (Caveolins)
RN  - 0 (Membrane Proteins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Acylation
MH  - Bradykinin/pharmacology
MH  - Calmodulin/metabolism
MH  - Caveolin 1
MH  - *Caveolins
MH  - Endothelium, Vascular/*enzymology
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase/drug effects/genetics/*physiology
MH  - Nitric Oxide Synthase Type III
MH  - *Signal Transduction
RF  - 33
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - S0100-879X(99)03201106 [pii]
AID - 10.1590/s0100-879x1999001100006 [doi]
PST - ppublish
SO  - Braz J Med Biol Res. 1999 Nov;32(11):1361-6. doi:
      10.1590/s0100-879x1999001100006.