| Cytoprotective effects of albumin, nitrosated or reduced, in cultured rat pulmonary vascular cells. | |
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MedLine Citation:
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PMID: 21239532 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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S-nitrosoalbumin (SNO-Alb) has been shown to be an efficacious cytoprotective molecule in acute lung injury, as well as ischemia-reperfusion injury in heart and skeletal muscle. Nonetheless, limited information is available on the cellular mechanism of such protection. Accordingly, we investigated the protective effects of SNO-Alb [ and its denitrosated congener, reduced albumin (SH-Alb) ] on tert-butyl hydroperoxide (tBH)-mediated cytotoxicity in cultured rat pulmonary microvascular endothelial cells (RPMEC), as well as hydrogen sulfide (H(2)S)-mediated cytotoxicity in rat pulmonary artery smooth muscle cells (RPASMC). We noted that tBH caused a concentration-dependent necrosis in RPMEC, and pretreatment of RPMEC with SNO-Alb dose-dependently decreased the sensitivity of these cells to tBH. A component of SNO-Alb cytoprotection was sensitive to N(G)-nitro-L-arginine methyl ester and was associated with activation of endothelial nitric oxide synthase (eNOS), phenomena that could be reproduced with pretreatment with SH-Alb. Exogenous H(2)S caused concentration-dependent apoptosis in RPASMC due to activation of ERK1/2 and p38, as well as downregulation of Bcl-2. Pretreatment with SNO-Alb reduced H(2)S-mediated apoptosis in a concentration-dependent manner that was associated with SNO-Alb-mediated inhibition of activation of ERK1/2 and p38. Pretreatment with SNO-Alb reduced toxicity of 1 mM sodium hydrosulfide in an N(G)-nitro-L-arginine methyl ester-sensitive fashion in RPASMC that expressed gp60 and neuronal NOS and was capable of transporting fluorescently labeled SH-Alb. Therefore, SNO-Alb is cytoprotective against models of oxidant-induced necrosis (tBH) and inhibitors of cellular respiration and apoptosis (H(2)S) in both pulmonary endothelium and smooth muscle, respectively, and a component of such protection can be attributed to a SH-Alb-mediated activation of constitutive NOS. |
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Authors:
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Hui-Hua Li; Jing Xu; Karla J Wasserloos; Jin Li; Yulia Y Tyurina; Valerian E Kagan; Xiaorong Wang; Alex F Chen; Zhao-Qian Liu; Detcho Stoyanovsky; Bruce R Pitt; Li-Ming Zhang |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-01-14 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 300 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-31 Completed Date: 2011-09-15 Revised Date: 2012-04-02 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L526-33 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects Arteries / cytology Cells, Cultured Cytoprotection / drug effects* Endocytosis / drug effects Endothelial Cells / cytology*, drug effects*, enzymology Humans Hydrogen Sulfide / pharmacology Lung / blood supply* Microvessels / cytology Myocytes, Smooth Muscle / cytology, drug effects Necrosis / pathology Nitric Oxide Synthase Type III / metabolism Nitrosation / drug effects Nitroso Compounds / pharmacology* Oxidation-Reduction / drug effects Rats Serum Albumin, Bovine / pharmacology* tert-Butylhydroperoxide / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL-094488/HL/NHLBI NIH HHS; HL-70755/HL/NHLBI NIH HHS; K08 HL79456-01A1/HL/NHLBI NIH HHS; P50 GM53789/GM/NIGMS NIH HHS; R37 HL65697/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nitroso Compounds; 0/S-nitrosoalbumin; 0/Serum Albumin, Bovine; 75-91-2/tert-Butylhydroperoxide; 7783-06-4/Hydrogen Sulfide; EC 1.14.13.39/Nitric Oxide Synthase Type III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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