Cytoprotective effects of albumin, nitrosated or reduced, in cultured rat pulmonary vascular cells.
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.
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Hui-Hua
HH
Li
Jing
J
Xu
Karla J
KJ
Wasserloos
Jin
J
Li
Yulia Y
YY
Tyurina
Valerian E
VE
Kagan
Xiaorong
X
Wang
Alex F
AF
Chen
Zhao-Qian
ZQ
Liu
Detcho
D
Stoyanovsky
Bruce R
BR
Pitt
Li-Ming
LM
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001158:Arteries / Q000166:cytology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D055806:Microvessels / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D009336:Necrosis / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D015538:Nitrosation / Q000187:drug effects; D009603:Nitroso Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D009603:Nitroso Compounds; C091665:S-nitrosoalbumin; D012710:Serum Albumin, Bovine; D020122:tert-Butylhydroperoxide; D052250:Nitric Oxide Synthase Type III; D006862:Hydrogen Sulfide
Biochemistry. 1999 Aug 17;38(33):10691-8
10451363
Environ Health Perspect. 1994 Dec;102 Suppl 10:17-24
7705293
Curr Opin Chem Biol. 2002 Dec;6(6):779-85
12470731
J Endotoxin Res. 2002;8(1):17-26
11981442
Antioxid Redox Signal. 2010 May 1;12(9):1061-4
19845469
Am J Physiol Cell Physiol. 2007 Apr;292(4):C1263-71
17092994
Science. 2005 Apr 22;308(5721):518
15845845
Arch Biochem Biophys. 1989 Mar;269(2):390-9
2919876
EMBO J. 2001 Nov 1;20(21):6008-16
11689441
Heart Vessels. 2004 Mar;19(2):75-80
15042391
Nat Chem Biol. 2005 Sep;1(4):223-32
16408039
Exp Biol Med (Maywood). 2006 Oct;231(9):1507-15
17018873
Crit Rev Toxicol. 1984;13(1):25-97
6378532
Naunyn Schmiedebergs Arch Pharmacol. 2009 Mar;379(3):281-90
18854985
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):250-4
8552615
Toxicol Appl Pharmacol. 1990 May;103(3):482-90
2160136
Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L243-9
11404267
J Cereb Blood Flow Metab. 2003 Jan;23(1):51-61
12500091
Cell Calcium. 2005 Jan;37(1):87-96
15541467
Circ Res. 2001 Jun 8;88(11):1210-5
11397789
J Am Chem Soc. 2005 Nov 16;127(45):15815-23
16277524
J Heart Lung Transplant. 2005 Dec;24(12):2226-34
16364875
Am J Physiol Cell Physiol. 2008 Apr;294(4):C1012-20
18287333
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9539-44
11493694
FASEB J. 2004 Nov;18(14):1782-4
15371330
Biochemistry. 2007 Jul 17;46(28):8472-83
17580965
Am J Physiol Lung Cell Mol Physiol. 2006 Sep;291(3):L457-65
16603592
Am J Respir Cell Mol Biol. 1992 Nov;7(5):471-6
1384580
Crit Care. 2009;13(3):213
19519960
Circulation. 2002 Jun 25;105(25):3032-8
12081999
Circ Res. 2006 Oct 13;99(8):870-7
16973909
J Biol Chem. 1997 May 9;272(19):12328-41
9139677
Shock. 2004 Feb;21(2):165-9
14752291