The antioxidant N-2-mercaptopropionyl glycine attenuates left ventricular hypertrophy in in vivo murine pressure-overload model
Moto-o Date, MD, PhD*,
Takashi Morita, MD ,
Nobushige Yamashita, MD, PhD*,
Kazuhiko Nishida, MD, PhD,
Osamu Yamaguchi, MD*,
Yoshiharu Higuchi, MD*,
Shinichi Hirotani, MD,
Yasushi Matsumura, MD, PhD ,
Masatsugu Hori, MD, PhD, FACC*,
Michihiko Tada, MD, PhD, FACC and
Kinya Otsu, MD, PhD*,*
* Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Pathophysiology, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Medical Information Science, Osaka University Graduate School of Medicine, Osaka, Japan
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Figure 1 Effect of N-2-mercaptopropionyl glycine (MPG) on cardiac hypertrophy induced by transverse aortic constriction (TAC). After the TAC procedure, mice received MPG twice daily intraperitoneally, were sacrificed seven days after TAC, and their hearts were removed and photographed (A). The hearts were histologically examined by hematoxylin-eosin and Masson trichrome stains (B). Control TAC = vehicle-treated TAC-operated mice; MPG TAC = MPG-treated TAC-operated mice; Sham = vehicle-treated sham-operated mice.
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Figure 2 Effect of N-2-mercaptopropionyl glycine (MPG) on atrial natriuretic factor (ANF) mRNA expression. Total RNA was isolated from hearts treated with (+) or without (–) MPG and analyzed for expression of ANF mRNA by northern blot. A representative northern blot analysis result is shown in the upper panel. Sham = sham-operated mice; TAC = TAC-operated mice. Lower panel shows the quantitative analysis of ANF mRNA expression relative to ß-actin mRNA based on densitometric measurements on northern blot. Data are expressed as mean ± SEM (n = 3). Two-way analysis for variance (ANOVA) was used to test significance, with one factor being sham versus TAC operation and the other factor being vehicle versus MPG treatment. As we faced a significant interaction, we have analyzed the data among groups by one-way ANOVA and Tukey-Kramer’s post hoc test.
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Figure 3 Effect of N-2-mercaptopropionyl glycine (MPG) on heme oxygenase (HO)-1 mRNA expression. Total RNA was isolated from hearts treated with (+) or without (–) MPG and analyzed for expression of HO-1 by northern blot. A representative northern blot analysis result is shown. Sham = sham-operated mice; TAC = transverse aortic constriction (TAC)-operated mice. Lower panel shows the quantitative analysis of HO-1 mRNA expression relative to ß-actin mRNA based on densitometric measurements on northern blot. Data are expressed as mean ± SEM (n = 3). Control Sham = vehicle-treated sham-operated mice; control TAC = vehicle-treated TAC-operated mice; MPG sham = MPG-treated sham-operated mice; MPG TAC = MPG-treated TAC-operated mice. Two-way analysis for variance (ANOVA) was used to test significance, with one factor being sham versus TAC operation and the other factor being vehicle versus MPG treatment. As we faced a significant interaction, we have analyzed the data among groups by one-way ANOVA with Tukey-Kramer’s post hoc test.
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Figure 4 Effect of N-2-mercaptopropionyl glycine (MPG) on transverse aortic constriction (TAC)-induced changes in lipid peroxidation. One week after the operation, mouse hearts were homogenized and subjected to a lipid peroxidation assay (n = 4). Control sham = vehicle-treated sham-operated mice; control TAC = vehicle-treated TAC-operated mice; MDA = malonaldehyde; MPG sham = MPG-treated sham-operated mice; MPG TAC = MPG-treated TAC-operated mice. Data are expressed as mean ± SEM. Two-way analysis for variance (ANOVA) was used to test significance, with one factor being sham versus TAC operation and the other factor being vehicle versus MPG treatment. As we faced a significant interaction, we have analyzed the data among all combination of groups by one-way ANOVA with Tukey-Kramer’s post hoc test.
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Figure 5 Effect of N-2-mercaptopropionyl glycine (MPG) on transverse aortic constriction (TAC)-induced changes in antioxidant enzyme activities. One week after the operation, mouse hearts were homogenized and subjected to superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase activity assays (n = 4). Control sham = vehicle-treated sham-operated mice; control TAC = vehicle-treated TAC-operated mice; MPG sham = MPG-treated sham-operated mice; MPG TAC = MPG-treated TAC-operated mice. Data are expressed as mean ± SEM. Two-way ANOVA indicated significant difference between TAC versus sham-operated mice, but not vehicle and MPG-treated mice in SOD and GSHPx activities without significant interaction. There were no significant differences in catalase activity between TAC and sham-operated groups and between vehicle and MPG-treated groups.
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