PMID- 21037226
OWN - NLM
STAT- MEDLINE
DCOM- 20110128
LR  - 20211020
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 300
IP  - 1
DP  - 2011 Jan
TI  - Mechanisms related to NO-induced motility in differentiated rat aortic smooth 
      muscle cells.
PG  - H101-8
LID - 10.1152/ajpheart.00342.2010 [doi]
AB  - Nitric oxide (NO) is thought to play an important role as an inhibitor of 
      vascular cell proliferation, motility, and neointima formation. This effect is 
      mediated, in part, via the upregulation of protein tyrosine phosphatase (PTP)1B. 
      Conversely, studies have reported that in presumably hyperinsulinemic mice fed a 
      high-fat diet, NO enhances vascular remodeling, whereas a deficit of NO 
      attenuates vascular remodeling. We have reported that in differentiated cultured 
      smooth muscle cells treated with insulin, NO induces a motogenic effect that is 
      dependent on Src homology-2 domain PTP 2 (SHP2) upregulation. In the present 
      study, we describe novel mechanisms relevant to the motogenic effect of NO. 
      Treatment of cultured cells with the selective angiontensin type 1 receptor 
      antagonist losartan, but not with the selective angiotensin type 2 receptor 
      antagonist PD-123319, blocked the comotogenic capacity of NO and insulin. Insulin 
      and NO increased the secretion of ANG II into the culture media by 2- and 
      2.5-fold (P < 0.05), respectively, whereas treatment of cells with ANG II 
      uncovered the motogenic effect of NO (1.4-fold above control, P < 0.05) and 
      decreased the levels of PTP1B to 45% of control (P < 0.05). Suppression of PTP1B 
      function was sufficient to uncover the motogenic effect of NO. The capacity of 
      insulin to suppress PTP1B activity was blocked by losartan, implicating ANG II 
      function in mediating this effect. Both insulin and ANG II induced the 
      upregulation of phosphatidyl inositol 3-kinase (PI3K)-delta by two- to threefold (P < 
      0.05), and this effect was both necessary and sufficient to uncover NO-induced 
      motogenesis. Finally, suppression of PTP1B function potentiated, whereas 
      overexpression of PTP1B inhibited, SHP2-induced motogenesis. These results 
      support the hypothesis that the comotogenic effect of insulin and NO occurs via 
      an ANG II-mediated effect involving the suppression of PTP1B and upregulation of 
      PI3K-delta and SHP2.
FAU - Pu, Qinghua
AU  - Pu Q
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      Tennessee 38163, USA.
FAU - Zhuang, Daming
AU  - Zhuang D
FAU - Thakran, Shalini
AU  - Thakran S
FAU - Hassid, Aviv
AU  - Hassid A
LA  - eng
GR  - HL-63886/HL/NHLBI NIH HHS/United States
GR  - HL-72902/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20101029
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Angiotensin II Type 2 Receptor Blockers)
RN  - 0 (Imidazoles)
RN  - 0 (Insulin)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Small Interfering)
RN  - 11128-99-7 (Angiotensin II)
RN  - 130663-39-7 (PD 123319)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Analysis of Variance
MH  - Angiotensin II/metabolism
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology
MH  - Angiotensin II Type 2 Receptor Blockers/pharmacology
MH  - Animals
MH  - Aorta, Thoracic/cytology/drug effects/*metabolism
MH  - Cell Movement/drug effects/*physiology
MH  - Cells, Cultured
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Imidazoles/pharmacology
MH  - Insulin/metabolism/*pharmacology
MH  - Losartan/pharmacology
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/drug effects/*metabolism
MH  - Myocytes, Smooth Muscle/cytology/drug effects/*metabolism
MH  - Nitric Oxide/metabolism/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism
MH  - Pyridines/pharmacology
MH  - RNA, Small Interfering
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Up-Regulation
PMC - PMC3023252
EDAT- 2010/11/03 06:00
MHDA- 2011/02/01 06:00
PMCR- 2012/01/01
CRDT- 2010/11/02 06:00
PHST- 2010/11/02 06:00 [entrez]
PHST- 2010/11/03 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - ajpheart.00342.2010 [pii]
AID - H-00342-2010 [pii]
AID - 10.1152/ajpheart.00342.2010 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H101-8. doi: 
      10.1152/ajpheart.00342.2010. Epub 2010 Oct 29.