Peroxynitrite inhibits the expression of Giα protein and adenylyl cyclase signaling in vascular smooth muscle cells

2008 ◽  
Vol 294 (2) ◽  
pp. H775-H784 ◽  
Author(s):  
Marcel Bassil ◽  
Yuan Li ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
P38 Map Kinase ◽  
Nitric Oxide Donor ◽  
Dependent Manner

We previously showed that S-nitroso- N-acetylpenicillamine, a nitric oxide donor, decreased the levels and functions of Giα proteins by formation of peroxynitrite (ONOO−) in vascular smooth muscle cells (VSMC). The present studies were undertaken to investigate whether ONOO− can modulate the expression of Giα protein and associated adenylyl cyclase signaling in VSMC. Treatment of A-10 and aortic VSMC with ONOO− for 24 h decreased the expression of Giα-2 and Giα-3, but not Gsα, protein in a concentration-dependent manner; expression was restored toward control levels by 111Mn-tetralis(benzoic acid porphyrin) and uric acid, but not by 1 H[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one (ODQ) and KT-5823. cGMP levels were increased by ∼50% and 150% by 0.1 and 0.5 mM ONOO−, respectively, and attenuated toward control levels by ODQ. In addition, 0.5 mM ONOO− attenuated the inhibition of adenylyl cyclase by ANG II and C-type atrial natriuretic peptide (C-ANP4–23), as well as the inhibition of forskolin-stimulated adenylyl cyclase activity by GTPγS, whereas, the Gs-mediated stimulations were augmented. In addition, 0.5 mM ONOO− decreased phosphorylation of ERK1/2 and p38 MAP kinase and enhanced JNK phosphorylation but did not affect AKT1/3 phosphorylation. These results suggest that ONOO− decreased the expression of Gi proteins and associated functions in VSMC through a cGMP-independent mechanism and may involve the MAP kinase signaling pathway.

Thrombin-induced MCP-1 Expression Involves Activation of the p22phox-containing NADPH Oxidase in Human Vascular Smooth Muscle Cells

2001 ◽  
Vol 85 (06) ◽  
pp. 1104-1110 ◽  
Author(s):  
C. Viedt ◽  
K. Nguyen ◽  
S. Beer ◽  
J. Kreuzer ◽  
R. Busse ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Nadph Oxidase ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Antisense Oligonucleotides ◽  
Muscle Cells ◽  
P38 Map Kinase ◽  
Ros Generation

SummaryActivation of vascular smooth muscle cells (VMSC) by thrombin induces the expression of the chemokine, monocyte chemoattractant protein-1 (MCP-1). We investigated in cultured human and rat VSMC whether reactive oxygen species (ROS) derived from the vascular NADPH oxidase contribute to this effect. Exposure of cultured VSMC to thrombin rapidly increased ROS formation, phosphorylation of p38 MAP kinase as well as the expression of MCP-1. Specific inhibition of the p22phox subunit of the vascular NADPH oxidase using either p22phox neutralizing antibody or p22phox antisense oligonucleotides attenuated thrombin-induced ROS generation. Furthermore, thrombininduced p38 MAP kinase activation as well as MCP-1 expression were impaired by antioxidants as well as by p22phox antisense oligonucleotides. Inhibition of p38 MAP kinase diminished the thrombin-induced expression of MCP-1. Conclusion: Thrombin, by activating a p22phoxcontaining NADPH oxidase, elicits ROS generation and activation of p38 MAP kinase in VSMC. The subsequent induction of MCP-1 expression highligts the crucial role of the p22phox-containing NADPH oxidase in thrombin-induced signal transduction in VSMC.

Hypoxia activates β1-integrin via ERK 1/2 and p38 MAP kinase in human vascular smooth muscle cells

2002 ◽  
Vol 296 (4) ◽  
pp. 890-896 ◽  
Author(s):  
Florian Blaschke ◽  
Philipp Stawowy ◽  
Stephan Goetze ◽  
Oliver Hintz ◽  
Michael Gräfe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
P38 Map Kinase ◽  
Β1 Integrin

scholarly journals Altered PDGF-BB–Induced p38 MAP Kinase Activation in Diabetic Vascular Smooth Muscle Cells

2004 ◽  
Vol 24 (11) ◽  
pp. 2095-2101 ◽  
Author(s):  
Hiroshi Yamaguchi ◽  
Masahiko Igarashi ◽  
Akihiko Hirata ◽  
Naoko Sugae ◽  
Hiromi Tsuchiya ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
P38 Map Kinase ◽  
Kinase Activation

Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK

2009 ◽  
Vol 296 (6) ◽  
pp. H1859-H1867 ◽  
Author(s):  
Maria Arejian ◽  
Yuan Li ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Time Dependent ◽  
Dependent Manner ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

We have earlier shown that the treatment of A10 vascular smooth muscle cells with S-nitroso- N-acetyl-penicillamine (SNAP); nitric oxide donor (NO) for 24 h decreased the expression of natriuretic peptide receptor C (NPR-C) and adenylyl cyclase signaling. The present study was undertaken to examine the implication of different signaling mechanisms in a NO-induced response. The treatment of A10 vascular smooth muscle cells with SNAP decreased the expression of NPR-C and Giα proteins in a time-dependent manner. The expression of Giα proteins was decreased at 6 h, whereas the expression of NPR-C was attenuated at 2 h. The NPR-C-mediated inhibition of adenylyl cyclase was attenuated (∼50%) after 2 h of treatment and was completely abolished after 6 h of treatment. The decreased expression of NPR-C and NPR-C-mediated attenuation of adenylyl cyclase after 2 h of treatment was reversed to control levels by PD-98059, a MEK inhibitor. SNAP also modulated the ERK1/2 phosphorylation in a time-dependent manner; an increase was observed up to 2 h, and, thereafter, the ERK1/2 phosphorylation was decreased. On the other hand, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823 inhibitor of soluble guanylyl cyclase and protein kinase G, respectively, and Mn(III)tetrakis(4-benzoic acid)porphyrin, a scavenger of peroxynitrite, were unable to restore the SNAP-induced decreased expression of NPR-C protein and increased ERK1/2 phosphorylation to control levels. However, the decreased levels of phosphorylated ERK1/2 and Giα proteins were restored to control levels by 8-bromo-cAMP. These results indicate that a temporal relationship follows between a NO-induced decreased expression of NPR-C and Giα proteins. The decreased expression of NPR-C is mediated through cGMP-independent but MAPK-dependent pathway, whereas NO-induced decreased levels of cAMP may contribute to the decreased activation of MAPK and thereby decreased the expression of Giα proteins.

15d-PGJ2 stimulates HO-1 expression through p38 MAP kinase and Nrf-2 pathway in rat vascular smooth muscle cells

2007 ◽  
Vol 223 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Hyun-Joung Lim ◽  
Kuy-Sook Lee ◽  
Seahyoung Lee ◽  
Jin-Hee Park ◽  
Hye-Eun Choi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
P38 Map Kinase

scholarly journals RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1748
Author(s):  
Eda Demirel ◽  
Caroline Arnold ◽  
Jaspal Garg ◽  
Marius Andreas Jäger ◽  
Carsten Sticht ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Genetic Ablation ◽  
Variable Expression ◽  
Arterial Blood

The regulator of G-protein signaling 5 (RGS5) acts as an inhibitor of Gαq/11 and Gαi/o activity in vascular smooth muscle cells (VSMCs), which regulate arterial tone and blood pressure. While RGS5 has been described as a crucial determinant regulating the VSMC responses during various vascular remodeling processes, its regulatory features in resting VSMCs and its impact on their phenotype are still under debate and were subject of this study. While Rgs5 shows a variable expression in mouse arteries, neither global nor SMC-specific genetic ablation of Rgs5 affected the baseline blood pressure yet elevated the phosphorylation level of the MAP kinase ERK1/2. Comparable results were obtained with 3D cultured resting VSMCs. In contrast, overexpression of RGS5 in 2D-cultured proliferating VSMCs promoted their resting state as evidenced by microarray-based expression profiling and attenuated the activity of Akt- and MAP kinase-related signaling cascades. Moreover, RGS5 overexpression attenuated ERK1/2 phosphorylation, VSMC proliferation, and migration, which was mimicked by selectively inhibiting Gαi/o but not Gαq/11 activity. Collectively, the heterogeneous expression of Rgs5 suggests arterial blood vessel type-specific functions in mouse VSMCs. This comprises inhibition of acute agonist-induced Gαq/11/calcium release as well as the support of a resting VSMC phenotype with low ERK1/2 activity by suppressing the activity of Gαi/o.

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