Evidence-based Practice for the Use of N-acetylcysteine

Marthaler, Maureen T.; Keresztes, Patricia

doi:10.1097/00003465-200411000-00008

Cited by 4 publications

(1 citation statement)

References 18 publications

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“…It is thought that NAC, in its role as a precursor to L-cysteine and glutathione, protects cell membranes against lipid peroxidation and protein oxidation. 25 Tempol, in contrast, predominantly acts as a superoxide dismutase mimic and therefore acts upstream of H 2 O 2 production. 26 These described mechanisms of action are in general agreement with the present study which showed that tempol failed to affect phosphorylation induced by exogenous H 2 O 2 , but was almost equally potent as NAC in decreasing PDGF-induced responses.…”

Section: December 2006mentioning

confidence: 99%

Antioxidants Relieve Phosphatase Inhibition and Reduce PDGF Signaling in Cultured VSMCs and in Restenosis

Kappert

Sparwel

Sandin

et al. 2006

ATVB

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Objective-Growth factor-and reactive oxygen species (ROS)-induced activation of VSMCs is involved in vascular disease. This study investigates whether inhibitory oxidation of protein tyrosine phosphatases (PTPs) contributes to signaling in VSMCs in vitro and in vivo, and analyzes whether ROS-and growth factor-dependent vascular smooth muscle cell (VSMC) signaling is blunted by antioxidants that are able to activate oxidized PTPs. Methods and Results-Signaling induced by H 2 O 2 and platelet-derived growth factor (PDGF) was analyzed in VSMCs with or without the antioxidants N-acetyl-cysteine (NAC) and tempol. Effects of antioxidants on PDGF-stimulated chemotaxis and proliferation were determined. In vivo effects of antioxidants were analyzed in the rat carotid balloon-injury model, by analyzing neointima formation, cell proliferation, PDGF ␤-receptor status, and PTP expression and activity. NAC treatment prevented H 2 O 2 -induced PTP inhibition, and reduced H 2 O 2 -and ligand-induced PDGF ␤-receptor phosphorylation, PDGF-induced proliferation, and chemotaxis of VSMCs. Antioxidants inhibited neointima formation and reduced PDGF receptor phosphorylation in the neointima and also increased PTP activity. Key Words: restenosis Ⅲ VSMC Ⅲ protein tyrosine phosphatase Ⅲ platelet-derived growth factor Ⅲ neointima formation V ascular injury induces oxidative stress and elevated production of reactive oxygen species (ROS) in the vessel wall. 1,2 Moreover, ROS are produced and act as second messengers as part of the signaling of receptor tyrosine kinases (RTKs) (reviewed in references 3,4 ), which are activated after vascular injury. The most important ROS for pathological conditions are superoxide (O2 Ϫ ) and hydrogen peroxide (H 2 O 2 ). Inhibition of ROS reduce vessel remodeling and restenosis. 5 The underlying mechanisms remain incompletely understood. Conclusion-PTP-inhibitionPDGF ␤-receptor activation contributes significantly to vascular smooth muscle cell (VSMC) proliferation and migration, which is a hallmark of vascular diseases such as atherosclerosis and restenosis. PDGF ligands and receptors are significantly upregulated in atherosclerotic plaques. Moreover, PDGF ␤-receptor antagonists inhibit atherogenesis and restenosis in various models. 6 PDGF ␤-receptors and other tyrosine kinases involved in VSMC proliferation and migration are regulated by protein tyrosine phosphatases (PTPs). 7 PTPs which have been identified as negative regulators of PDGF ␤-receptors include the receptor-like PTP DEP-1, and the cytosolic phosphatases TC-PTP and PTP-1B (reviewed in reference 8 ). However, there are also indications that some PTPs, such as SHP-2, act as positive mediators of PDGF ␤-receptor signaling. The expression pattern of PTPs in VSMCs remains incompletely characterized. However, expression of PDGF receptor-antagonizing PTPs such as DEP-1, TC-PTP, and PTP-1B has been confirmed in previous studies. 9 PTPs themselves are subject to multiple regulatory mechanisms. Reversible oxidation of the active site cysteine residu...

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Section: December 2006mentioning

confidence: 99%