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Methamphetamine‐induced oxidative‐stress modifies contractile and mitochondrial proteins in the heart
Author(s) -
Lord Kevin C,
Shenouda Sylvia K,
McIlwain Elizabeth,
Pollman Megan,
Lucchesi Pamela A.,
Varner Kurt J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.747.11
Subject(s) - oxidative stress , methamphetamine , meth , endocrinology , medicine , contractility , oxidative phosphorylation , chemistry , mitochondrion , pharmacology , biochemistry , monomer , organic chemistry , acrylate , polymer
We reported that binge administration of methamphetamine (METH) produces eccentric left ventricular (LV) dilation, systolic and diastolic dysfunction. Although the mechanisms underlying these deficits are unknown, our data using the antioxidant tempol, suggests that oxidative stress plays a significant role. We hypothesized that the increase in oxidative stress produces LV dysfunction via the posttranslational modification of myocardial proteins. Male Sprague‐Dawley rats were treated with METH or saline (2×d for 4 d), followed by a 10 day drug‐free period (“binge”). One day after the fourth binge, eccentric dilation was observed in METH‐treated rats. Proteomic analysis showed that compared to saline, METH‐treated rats had increased nitration and oxidation of contractile (actin, alpha‐beta crystalline, myosin light chain) and mitochondrial (cytochrome C reductase, F1 ATP synthase, NADH dehydrogenase) proteins. Electrically stimulated (1 Hz) adult LV myocytes from METH‐treated rats exhibited decreased contractility and impaired relaxation compared to control. Post‐stimulus [Ca 2+ ] i was decreased while its return to baseline was unaffected. In conclusion, the LV dysfunction produced by METH may be due to the redox modification of contractile and/or mitochondrial proteins but not calcium handling proteins. Support: AHA 655769, NIH P20‐ RR018766