β-Actin: A Regulator of NOS-3

Abstract

Beta-actin is traditionally considered a structural protein that organizes and maintains the shape of nonmuscle cells, although data now indicate that beta-actin is also a signaling molecule. beta-actin is directly associated with nitric oxide synthase type 3 (NOS-3) in endothelial cells and platelets, and this interaction increases NOS-3 activity and the affinity of NOS-3 for heat shock protein 90 kD (Hsp90). The beta-actin-induced increase in NOS-3 activity may be caused directly by beta-actin, the binding of Hsp90 to NOS-3, or both. Alterations in the interaction between beta-actin and NOS-3 could be caused by changes either in the availability of beta-actin or in the affinity of NOS-3 for beta-actin, and these alterations probably contribute to vascular complications and platelet aggregation. Studies examining the interactions between NOS-3, beta-actin, and Hsp90 could potentially lead to the discovery of effective peptides for the treatment of diseases associated with impaired NOS-3 activity and nitric oxide release, such as systemic and pulmonary hypertension, atherosclerosis, and thrombotic diseases.

Polymorphisms of Angiotensin Converting Enzyme and Nitric Oxide Synthase 3 Genes as Risk Factors of High-Altitude Pulmonary Edema: A Case-Control Study and Meta-Analysis

“…Single-locus analysis suggested a positive association of the G allele of rs8066114 and the T allele of rs4461142 with HAPE under the dominant model of inheritance. Although no significant associations were found for any of the other four polymorphisms, their corre- (Ahsan et al 2006;Su et al 2007), which may lead to HAPE. Although the association between NOS3 gene variants and HAPE susceptibility has been previously assessed in a number of studies, the results have not been consistent, especially for the NOS3 rs1799983 (G894T) polymorphism (Droma et al 2002;Weiss et al 2003;Ahsan et al 2004Ahsan et al , 2006Sun et al 2010).…”

β-Actin Association with Endothelial Nitric-oxide Synthase Modulates Nitric Oxide and Superoxide Generation from the Enzyme

“…We have reported that the ␤-actin-binding site on eNOS protein is located at the oxygenase domain (6,7). The oxygenase domain is involved with superoxide generation when eNOS is eNOS-␤-Actin Interaction FEBRUARY 12, 2010 • VOLUME 285 • NUMBER 7…”

“…The synthesis of NO requires NADPH, tetrahydrobiopterin (BH 4 ), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and O 2 as cofactors and results in NO and the co-product L-citrulline (1). eNOS is tightly regulated by transcriptional, post-transcriptional, and post-translational mechanisms (5,6). Protein-protein interactions represent an important post-translational mechanism for eNOS regulation (5).…”

“…We have found that eNOS localized to the plasma membrane is colocalized with cortical F-actin. eNOS that is located in the perinuclear area (probably Golgi) is colocalized with G-actin (5)(6)(7)(8). eNOS and actin in endothelial cells can be co-immunoprecipitated, suggesting that eNOS is associated with ␤-actin protein (8).…”

Female Vascular Senescence

“…The triggering of endothelial signaling by mechanic forces seems to be mostly determined by the cytoskeleton, which represents a highly dynamic network that constantly assembles and disassembles, playing an active role in responding to mechanical stimuli (Wong et al, 1983). The cytoskeleton rearranges upon changes on stress and stretch and activates signaling molecules, such as NO production, that are capable to regulate vascular tone in order to keep homeostasis (Su et al, 2005;Su et al, 2007). An increase in arterial wall stiffening by aging could alter the impact of a mechanical stimulus, and therefore induce a significant reduction or dysfunction in the signaling pathways activated by shear stress (Kliche et al, 2011).…”