Page 1 Articles of 36 in PresS. Am J Physiol Heart Circ Physiol (July 14, 2006). doi:10.1152/ajpheart.00427.2006
H-00427-2006R1 Matsushima et al. Page 1
Overexpression of Glutathione Peroxidase Attenuates Myocardial Remodeling and Preserves Diastolic Function in Diabetic Heart Running title: GSHPx and diabetic heart
Shouji Matsushima, Shintaro Kinugawa, Tomomi Ide, Hidenori Matsusaka, Naoki Inoue, Yukihiro Ohta, Takashi Yokota, Kenji Sunagawa, Hiroyuki Tsutsui Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (SM, TI, HM, KS) and Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638 (SK,NI, YO, TY, HT), Japan
Supported in part by grants from the Ministry of Education, Science and Culture, Japan (No. 12670676, 14370230, 17390223, 17659223)
Address for correspondence: Hiroyuki Tsutsui, M.D., Ph.D. Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan Phone: +81-11-706-6970, FAX: +81-11-706-7874 e-mail:
[email protected]
Copyright Information Copyright © 2006 by the American Physiological Society.
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H-00427-2006R1 Matsushima et al. Page 2
Abstract Oxidative stress plays an important role in the structural and functional abnormalities of diabetic heart. Glutathione peroxidase (GSHPx) is a critical antioxidant enzyme which removes H2O2 both in the cytosol and mitochondia. We hypothesized that the overexpression of GSHPx gene could attenuate left ventricular (LV) remodeling in diabetes mellitus (DM). We induced DM by injection of streptozotocin (160 mg/kg, ip) in male GSHPx transgenic mice (TG+DM) and nontransgenic wild-type littermates (WT+DM). GSHPx activity was higher in the hearts of TG mice compared to WT mice with no significant changes in other antioxidant enzymes. LV thiobarbituric acid-reactive substances measured in TG+DM at 8 weeks were significantly lower than those in WT+DM (58±3 vs. 71±5 nmol/g, P
