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Nutrient-Gene Expression

Expression of Rat Hepatic 2-Amino-3-Carboxymuconate-6-Semialdehyde Decarboxylase Is Affected by a High Protein Diet and by Streptozotocin-Induced Diabetes

Atsushi Tanabe^*1, Yukari Egashira^*, Shin-Ichi Fukuoka, Katsumi Shibata^** and Hiroo Sanada^*

^* Graduate School of Science and Technology, Chiba University, 648 Matsudo, Matsudo, Chiba 271-8510, Japan; Division of Food Science and Biotechnology, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan; and ^** School of Human Cultures, University of Shiga Prefecture, 2500 Hassakacho, Hikone, Shiga 522-8533, Japan

¹To whom correspondence should be addressed. E-mail: atanabe{at}i.bekkoame.ne.jp.

In the tryptophan-niacin conversion, 2-amino-3-carboxymuconate-6-semiardehyde decarboxylase (ACMSD; formerly termed picolinic carboxylase) is an important enzyme regulating the generation of quinolinate. In a series of experiments, we investigated alterations of ACMSD expression in rats by feeding a high protein diet and by inducing diabetes with streptozotocin (STZ). Male Sprague–Dawley rats (5-wk-old) were fed a diet containing 40% casein for 11 d, and hepatic ACMSD activity and mRNA expression were determined at intervals. The enzyme activity had increased at d 2, and it continued to increase through d 11. ACMSD mRNA expression had increased at d 1 and the elevated levels were maintained through d 11. Shifting from the 40% casein diet to a 20% casein diet restored hepatic ACMSD activity and mRNA expression to normal levels within 5 d and 2 d, respectively. In another series of experiments, male Wistar rats were injected with STZ (50 mg/kg) and the time-course (d 0, 1, 2, 4, 8 and 14) of the change in hepatic ACMSD activity and mRNA expression were examined. The activity increased dramatically after d 4, while mRNA expression was significantly elevated at d 2, followed by slight increases through d 14. Insulin administration (2 U/12 h) reduced the elevated ACMSD activity and fully suppressed the elevated ACMSD mRNA expression due to STZ injection. These results indicated that the fluctuation of hepatic ACMSD mRNA expression was followed by that of ACMSD activity.

KEY WORDS: • 2-amino-3-carboxymuconate-6-semiardehyde decarboxylase • tryotophan-niacin metabolism • high protein diet • streptozotocin-diabetes • rats

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