Increased resistance to myocardial ischemia in the Brown Norway vs. Dahl S rat: role of nitric oxide synthase and Hsp90.

Increased resistance to myocardial ischemia in the Brown Norway vs. Dahl S rat: role of nitric oxide synthase and Hsp90.
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挪威棕色大鼠与达尔 S 大鼠相比,心肌缺血抵抗力增强:一氧化氮合酶和 Hsp90 的作用。

DOI:
10.1016/j.yjmcc.2005.02.005
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发表时间:
2005
期刊:
Journal of molecular and cellular cardiology.
影响因子:
--
通讯作者:
Baker,JohnE
Baker,JohnE
中科院分区:
--
文献类型:
--
作者:
Shi,Yang;Hutchins,William;Ogawa,Hitoshi;Chang,Chung-Che;PritchardJr,KirkwoodA;Zhang,Chenyang;Khampang,Pawjai;Lazar,Jozef;Jacob,HowardJ;Rafiee,Parvaneh;Baker,JohnE

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棕色挪威(BN/MCW)大鼠的心脏比达尔·S(SS/MCW)大鼠的心脏具有更强的抗缺血能力。我们确定了一氧化氮(·NO)是否与BN/MCW和SS/MCW心脏保护作用的增强有关。两个品系的心脏在缺血再灌流前分别给予单甲基-L-精氨酸(L-精氨酸)或S-亚硝基-谷胱甘肽(GSNO)处理。未治疗的BN/MCW心肌梗死面积比SS/MCW心肌梗死面积小63%。用L-NMA抑制一氧化氮合酶可增加BN/MCW心脏的梗塞面积,但不会进一步增加SS/MCW心脏的损伤。·NO供体GSNO可缩小SS/MCW大鼠心肌梗死面积,但对BN/MCW大鼠心脏无明显影响。BN/MCW大鼠血浆和心脏组织中的亚硝酸盐+硝酸盐含量分别比SS/MCW大鼠高80%和130%。这些数据表明,增加·NO的产生对BN/MCW心脏缺血损伤具有保护作用。实时荧光定量聚合酶链式反应显示两株病毒的NOS1、NOS2和NOS3同工酶转录本没有差异。Western分析检测到的唯一同工酶为NOS3。两株病毒的NOS3和HSP90蛋白表达水平相同。然而,在BN/MCW心脏中,HSP90与NOS3的关联性是SS/MCW心脏的两倍。用格尔达那霉素抑制HSP90-NOS3的相互作用可降低BN/MCW心脏对缺血的抵抗力,但对SS/MCW心脏无明显影响。SS/MW型心脏产生的N-ω-硝基-L-精氨酸甲酯抑制超氧化物歧化能力是BN/MW型心脏的三倍。这些结果表明,HSP90与NOS3联合使用增加了·NO的产生,降低了解偶联的NOS3的活性。我们得出结论,HSP90与NOS3的结合增加是BN/MCW心脏比SS/MCW心脏更耐缺血的主要机制。
Hearts from Brown Norway (BN/Mcw) rats are more resistant to ischemia than hearts from Dahl S (SS/Mcw) rats. We determined whether nitric oxide (·NO) is responsible for increased cardioprotection in BN/Mcw vs. SS/Mcw hearts. Hearts from the two strains were treated with NG-monomethyl-l-arginine (l-NMA) or S-nitrosoglutathione (GSNO) before ischemia and reperfusion. Infarct size in untreated BN/Mcw hearts was ~63% less than in SS/Mcw hearts. Inhibiting NOS with l-NMA increased infarct size in BN/Mcw hearts to that observed in untreated SS/Mcw hearts but did not further increase injury in SS/Mcw hearts. The ·NO donor GSNO decreased infarct size in SS/Mcw rats but had no effect on BN/Mcw hearts. Plasma and heart tissue from BN/Mcw rats contained 80% and 130% more nitrite+nitrate than that from SS/Mcw rats. These data suggest that increased ·NO production protects BN/Mcw hearts from ischemic injury. Real time PCR showed no differences in NOS1, NOS2 or NOS3 isozyme transcripts in the hearts from the two strains. NOS3 was the only isozyme detected by western analysis. Both strains exhibited the same level of NOS3 and hsp90 protein expression. However, hsp90 association with NOS3 in BN/Mcw hearts was increased twofold compared with SS/Mcw hearts. Inhibiting hsp90-NOS3 interaction with geldanamycin decreased the resistance to ischemia in BN/Mcw hearts but not in SS/Mcw hearts. SS/Mcw hearts also generated three times more Nω-nitro-l-arginine-methylester inhibitable superoxide than BN/Mcw hearts. These findings indicate that hsp90 with NOS3 increases ·NO production and decreases uncoupled NOS3 activity. We conclude increased association of hsp90 with NOS3 is a major mechanism by which BN/Mcw hearts are more resistant to ischemia than SS/Mcw hearts.
DOI: 10.1016/s0891-5849(00)00364-6
发表时间: 2000-10-15
影响因子: 7.4
作者:
Shi, Y;Pritchard, KA;Baker, JE
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发表时间: 2000-04-27
影响因子: 4.6
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发表时间: 1994-11
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影响因子: --
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Jean-Luc BalligandS;Dan Ungureanu-LongroisSg;William;-W.;Simmons;David Pimental;Tadeusz A. Malinskin;Matthias Kapturczakn;Ziad Tahan;Charles;Lowensteinll;Amy;DavidoP;Ralph;Kelly;Thomas;Smith;Thomas MichelSS
通讯作者: Jean-Luc BalligandS;Dan Ungureanu-LongroisSg;William;-W.;Simmons;David Pimental;Tadeusz A. Malinskin;Matthias Kapturczakn;Ziad Tahan;Charles;Lowensteinll;Amy;DavidoP;Ralph;Kelly;Thomas;Smith;Thomas MichelSS
心脏对慢性缺氧的适应通过增加一氧化氮的产生来增加对随后的缺血的耐受性。
DOI: 10.1007/978-1-4615-4863-8_25
发表时间: 1998
影响因子: --
作者:
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通讯作者: PritchardJr,KA