Nitric Oxide Induces Heme Oxygenase-1 Gene Expression and Carbon Monoxide Production in Vascular Smooth Muscle Cells
Houston VA Medical Center, TX 77030, USA. Circulation Research
(Impact Factor: 11.02).
05/1997; 80(4):557-64. DOI: 10.1161/01.RES.80.4.557
Since recent studies demonstrate that vascular smooth muscle cells synthesize two distinct guanylate cyclase-stimulatory gases, NO and CO, we examined possible regulatory interactions between these two signaling molecules. Treatment of rat aortic smooth muscle cells with the NO donors, sodium nitroprusside, S-nitroso-N-acetyl-penicillamine, or 3-morpholinosydnonimine, increased heme oxygenase-I (HO-1) mRNA and protein levels in a concentration and time-dependent manner. Both actinomycin D and cycloheximide blocked NO-stimulated HO-1 mRNA and protein expression. Nuclear run-on experiments demonstrated that NO donors increased HO-1 gene transcription between 3- and 6-fold. In contrast, NO donors had no effect on the stability of HO-1 mRNA. Incubation of vascular smooth muscle cells with the membrane-permeable cGMP analogues, dibutyryl cGMP and 8-bromo-cGMP, failed to induce HO-1 gene expression. Treatment of vascular smooth muscle cells with NO donors also stimulated the production and release of CO, as demonstrated by the CO-dependent increase in intracellular cGMP levels in coincubated platelets. Finally, incubating vascular smooth muscle cells with interleukin-1 beta and tumor necrosis factor-alpha induced NO synthesis and also significantly increased the level of HO-1 protein. The cytokine-stimulated production of both NO and HO-1 protein in smooth muscle cells was blocked by the NO synthase inhibitor methyl-L-arginine. These results demonstrate that exogenously administered or endogenously released NO stimulates HO-1 gene expression and CO production in vascular smooth muscle cells. The ability of NO to induce HO-catalyzed CO release from vascular smooth muscle cells provides a novel mechanism by which NO might modulate soluble guanylate cyclase and, thereby, vascular smooth muscle cell and platelet function.
Available from: Raffaella Sorrentino
- "Inhibits HO activity in vascular smooth muscle cell Durante et al., 1997; Hartsfield et al., 1997 BJP Gasotransmitters in erectile function/dysfunction the 3-mercaptopyruvate sulphurtransferase and the cysteine aminotransferase. For more details, see review by Wang (2012). "
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ABSTRACT: The ability to get and keep an erection is important to men for several reasons and the inability is called as erectile dysfunction (ED). ED started to be accepted as an early indicator for systemic endothelial dysfunction and subsequent of cardiovascular diseases. The role of nitric oxide (NO) in endothelial relaxation and erectile function is well accepted. The discovery of NO as small signaling gasotransmitter led to the investigation of the role of other endogenously derived gases, carbon monoxide (CO) and hydrogen sulfide (H2 S) in physiological and pathophysiological conditions. The role of NO and CO in sexual function and dysfunction has been investigated more extensively and recently the involvement of H2 S in erectile function has also been confirmed. In this review, we focused on the role of these 3 sister gasotransmitters in the physiology, pharmacology and pathophysiology of sexual function in man, specifically erectile function. We also reviewed the role of soluble guanylyl cyclase /cyclic GMP pathway as a common target of these gasotransmitters. Several studies proposed alternative therapies targeting different mechanisms in addition to phosphodiesterase-5 inhibition for ED treatment, since some patients do not respond to these drugs. This review highlights complementary and possible coordinated roles for these mediators and treatments targeting these gasotransmitters in erectile function/ED.
Available from: Elena Uyy (Puchianu)
- "159] CNCSIS-UEFISCSU and CARDIOPRO project ID:143, ERDF co-financed investment in RTDI for Competitiveness. to regulate vascular reactivity and blood pressure (Durante et al. 1997). Caveolae have been implicated in chronic inflammatory conditions and other pathologies including atherosclerosis, pulmonary dysfunctions, inflammatory bowel disease, muscular dystrophy and generalized dyslipidemia (Simionescu and Simionescu 1991; Simionescu and Antohe 2006; Chidlow and Sessa 2010; Uyy et al. 2010). "
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ABSTRACT: A high-lipid diet is one of the main risk factors in atherosclerosis and can induce changes in the composition of plasma membrane microdomains. In response, important functions such as vesicle trafficking, protein docking, signaling and receptor recognition are significantly altered. In particular, interactions of heat-shock proteins (Hsps), acting as danger signals, with components of the membrane microdomains can influence signaling pathways and the inflammatory response of cells. Our study focuses on the composition of detergent-resistant membrane (DRM) isolated from ApoE-/- mice fed a standard or high-fat diet with and without fluvastatin treatment versus appropriate controls. Biochemical studies, immunoblotting and liquid chromatography mass spectrometric analysis were performed to investigate whether the structural components (such as caveolin and cavin) of the detergent-resistant microdomains were correlated with the expression and secretion of stress-inducible Hsps (Hsp70 and Hsp90) and AKT phosphorylation in experimental atherosclerosis. ApoE-/- mice challenged with a high-fat diet developed extensive atherosclerotic plaques in lesion-prone areas. DRM harvested from hyperlipidemic animals showed a modified biochemical composition with cholesterol, glycerolipids, caveolin-1 and phospho-AKT being up-regulated, whereas cavin-1 and dynamin were down-regulated. The data also demonstrated the co-fractionation of Hsps with caveolin-1 in isolated DRM, expression being positively correlated with their secretion into blood serum. Statin therapy significantly attenuated the processes induced by the development of atherosclerosis in ApoE-/- mice under a high-fat diet. Thus, high-lipid stress induces profound changes in DRM biochemistry and modifies the cellular response, supporting the systemic inflammatory onset of atherosclerosis.
Available from: Mariane Tami Amano
- "Although CO activates cGMP, nitric oxide (NO) activates it more potently . The relationship between these two molecules seems to involve a complex negative feedback loop: NO induces HO-1 expression and consequently CO production , while conversely, HO-1 and CO inhibit NO synthesis activity [146,147]. "
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ABSTRACT: The number of organ and tissue transplants has increased worldwide in recent decades. However, graft rejection, infections due to the use of immunosuppressive drugs and a shortage of graft donors remain major concerns. Carbon monoxide (CO) had long been regarded solely as a poisonous gas. Ultimately, physiological studies unveiled the endogenous production of CO, particularly by the heme oxygenase (HO)-1 enzyme, recognizing CO as a beneficial gas when used at therapeutic doses. The protective properties of CO led researchers to develop uses for it, resulting in devices and molecules that can deliver CO in vitro and in vivo. The resulting interest in clinical investigations was immediate. Studies regarding the CO/HO-1 modulation of immune responses and their effects on various immune disorders gave rise to transplantation research, where CO was shown to be essential in the protection against organ rejection in animal models. This review provides a perspective of how CO modulates the immune system to improve transplantation and suggests its use as a therapy in the field.
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