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Effects of mild hyperhomocysteinemia on electron transport chain complexes, oxidative stress, and protein expression in rat cardiac mitochondria.

Abstract：

:Hyperhomocysteinemia (HHcy) is an independent risk factor of cardiovascular disease, but the mechanisms of tissue injury are poorly understood. In the present study, we investigated the effect of HHcy on rat heart function, activities electron transport chain (ETC) complexes, mitochondrial protein expression, and protein oxidative damage. HHcy was induced by subcutaneous injection of Hcy (0.45 μmol/g of body weight) twice a day for a period of 2 weeks. Performance of hearts excised after the Hcy treatment was examined according to the Langendorff method at a constant pressure. Left ventricular developed pressure, as well as maximal rates of contraction (+dP/dt) and relaxation (-dP/dt), was significantly depressed in HHcy rats. HHcy was accompanied by significant inhibition of ETC complexes II-IV, whereas activity of the complex I was unchanged. The decline in ETC activities was not associated with elevated protein oxidative damage, as indicated by unchanged protein carbonyl, thiol, and dityrosine contents. Moreover, the level of protein adducts with 4-hydroxynonenal was decreased in HHcy rats. Additionally, 2D-gel electrophoresis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry did not show alterations in contents of inhibited ETC complexes. However, mass spectrometry analyses identified 8 proteins whose expression was significantly increased by HHcy. These proteins are known to play important roles in the cellular stress response, bioenergetics, and redox balance. Altogether, the results suggest that oxidative damage and altered protein expression are not possible causes of ETC dysfunction in HHcy rats. Increased expression of the other mitochondrial proteins indicates a protective response to Hcy-induced myocardial injury.

journal_name

Mol Cell Biochem

journal_title

Molecular and cellular biochemistry

authors

Timkova V,Tatarkova Z,Lehotsky J,Racay P,Dobrota D,Kaplan P

doi

10.1007/s11010-015-2588-7

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

261-70

issue

1-2

eissn

0300-8177

issn

1573-4919

pii

10.1007/s11010-015-2588-7

journal_volume

411

pub_type

杂志文章

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Effects of mild hyperhomocysteinemia on electron transport chain complexes, oxidative stress, and protein expression in rat cardiac mitochondria.