Antioxidant enzyme gene expression in congestive heart failure following myocardial infarction

• Published in: Molecular and cellular biochemistry Vol. 251; no. 1-2; pp. 9 - 15
• Main Authors: Khaper, N, Kaur, K, Li, T, Farahmand, F, Singal, P K
• Format: Journal Article
• Language: English
• Published: Netherlands 01.09.2003
• Subjects: Animals; Antihypertensive Agents - therapeutic use; Antioxidants - metabolism; Catalase - genetics; Catalase - metabolism; Enzymes - genetics; Enzymes - metabolism; Gene Expression; Glutathione Peroxidase - genetics; Glutathione Peroxidase - metabolism; Heart Failure - etiology; Heart Failure - genetics; Heart Failure - metabolism; Heart Failure - physiopathology; Losartan - therapeutic use; Male; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocardium - enzymology; Myocardium - metabolism; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; RNA, Messenger - metabolism; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Time Factors; Transcription, Genetic
• ISSN: 0300-8177
• DOI: 10.1023/A:1025448908694

Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time.