scholarly journals NO Attenuates Insulin Signaling and Motility in Aortic Smooth Muscle Cells via Protein Tyrosine Phosphatase 1B–Mediated Mechanism

2002 ◽  
Vol 22 (7) ◽  
pp. 1086-1092 ◽  
Author(s):  
Nair Sreejayan ◽  
Yi Lin ◽  
Aviv Hassid
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Insulin Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Muscle Cells ◽  
Protein Tyrosine Phosphatase 1B ◽  
Aortic Smooth Muscle Cells ◽  
Protein Tyrosine ◽  
Aortic Smooth Muscle

scholarly journals Suppression of PKG by PDGF or nitric oxide in differentiated aortic smooth muscle cells: obligatory role of protein tyrosine phosphatase 1B

2011 ◽  
Vol 300 (1) ◽  
pp. H57-H63 ◽  
Author(s):  
Daming Zhuang ◽  
Poonam Balani ◽  
Qinghua Pu ◽  
Shalini Thakran ◽  
Aviv Hassid
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Muscle Cells ◽  
Protein Tyrosine Phosphatase 1B ◽  
Aortic Smooth Muscle Cells ◽  
Protein Tyrosine ◽  
Aortic Smooth Muscle

Treatment of aortic smooth muscle cells with PDGF induces the upregulation of protein tyrosine phosphatase 1B (PTP1B). PTP1B, in turn, decreases the function of several growth factor receptors, thus completing a negative feedback loop. Studies have reported that PDGF induces the downregulation of PKG as part of a repertoire of dedifferentiation of vascular smooth muscle cells. Other studies have reported that chronic nitric oxide (NO) treatment also induces the downregulation of PKG. In the present study, we tested the hypothesis that the downregulation of PKG by PDGF or NO in differentiated rat aortic smooth muscle cells can be attributed to the upregulation of PTP1B. We found that treatment with PDGF or NO induced an upregulation of PTP1B levels. Overexpression of PTP1B induced a marked downregulation of PKG mRNA and protein levels, whereas the expression of dominant negative PTP1B or short interfering RNA directed against PTP1B blocked the capacity of PDGF or NO to decrease PKG levels. We conclude that the upregulation of PTP1B by PDGF or NO is both necessary and sufficient to induce the downregulation of PKG via an effect on PKG mRNA levels.

NO increases protein tyrosine phosphatase activity in smooth muscle cells: relationship to antimitogenesis

1997 ◽  
Vol 272 (3) ◽  
pp. H1342-H1349 ◽  
Author(s):  
G. S. Dhaunsi ◽  
C. Matthews ◽  
K. Kaur ◽  
A. Hassid
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Protein Tyrosine ◽  
Aortic Smooth Muscle ◽  
Cyclic Monophosphate ◽  
Ptpase Activity

We investigated the mechanisms of NO-induced antimitogenesis in primary aortic smooth muscle cells from newborn rats. S-nitroso-N-acetylpenicillamine (SNAP), an NO-releasing agent, decreased basal and growth factor-stimulated DNA synthesis with a threshold effectiveness of 0.3-3 microM. A second NO-releasing agent, 3-morpholinosydnonimine-N-ethylcarbamide, a hydrolysis-resistant cyclic nucleotide, 8-bromo-guanosine 3',5'-cyclic monophosphate (8-BrcGMP), and atrial natriuretic peptides elicited a similar effect, whereas 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP) was ineffective, supporting the view that NO and cGMP, but not cAMP, mediated at least some of SNAP's antimitogenic effect. SNAP and 8-BrcGMP decreased the levels of phosphotyrosine, especially in proteins of 70-85 kDa and approximately 215 kDa molecular mass. SNAP decreased protein phosphotyrosine levels with a threshold effectiveness similar to that of its antimitogenic effect. Moreover, SNAP increased protein tyrosine phosphatase (PTPase) activity in cell homogenates, indicating that phosphotyrosine dephosphorylation was likely to be the result of increased PTPase activity. Peroxovanadate, a selective PTPase inhibitor, blocked the antimitogenic effect of 8-BrcGMP, suggesting that loss of protein phosphotyrosine and antimitogenesis were causally linked. These findings describe a potential mechanism for NO-induced antimitogenesis in aortic smooth muscle cells in primary culture.

Requirement of protein tyrosine phosphatase SHP2 for NO-stimulated vascular smooth muscle cell motility

2001 ◽  
Vol 281 (4) ◽  
pp. H1598-H1605 ◽  
Author(s):  
Claire Brown ◽  
Yi Lin ◽  
Aviv Hassid
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cell Motility ◽  
Protein Tyrosine Phosphatases ◽  
Muscle Cells ◽  
Adult Rats ◽  
Aortic Smooth Muscle Cells ◽  
Protein Tyrosine ◽  
Aortic Smooth Muscle ◽  
Protein Levels

We have previously reported that nitric oxide (NO) increases the motility of differentiated cultured primary aortic smooth muscle cells from adult rats. There is little information on the role of protein tyrosine phosphatases in vascular biology. One such phosphatase, Src homology 2 phosphatase 2 (SHP2), is essential for motility. We tested the hypothesis that NO increases SHP2 levels via a cGMP-mediated mechanism and that this effect is necessary for NO-stimulated cell motility. Here we report that two different NO donors increased SHP2 protein levels and enzyme activity. This effect was mimicked by several cGMP agonists and blocked by an inhibitor of guanylyl cyclase. Specific decrease of SHP2 protein levels via the use of antisense oligodeoxynucleotides (ODNs), but not several control ODNs attenuated the motogenic effect of NO, which indicates the involvement of SHP2 in NO-elicited motogenesis. S-nitroso- N-acetylpenicillamine failed to increase SHP2 protein levels in subcultured aortic smooth muscle cells. This provides a potential explanation for the lack of effect of NO on cell motility in dedifferentiated subcultured cells. These results support the hypothesis that NO-elicited upregulation of SHP2 via a cGMP-mediated pathway is necessary for NO-induced motogenesis in differentiated aortic smooth muscle cells.

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