In vivo role of aldehyde reductase

Motoko Takahashi, Satoshi Miyata, Junichi Fujii, Yoko Inai, Shigemitsu Ueyama, Motoko Araki, Tomoyoshi Soga, Reiko Fujinawa, Chiaki Nishitani, Shigeru Ariki, Takeyuki Shimizu, Tomomi Abe, Yoshito Ihara, Morimitsu Nishikimi, Yasunori Kozutsumi, Naoyuki Taniguchi, Yoshio Kuroki

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Aldehyde reductase (AKR1A; EC 1.1.1.2) catalyzes the reduction of various types of aldehydes. To ascertain the physiological role of AKR1A, we examined AKR1A knockout mice. Methods: Ascorbic acid concentrations in AKR1A knockout mice tissues were examined, and the effects of human AKR1A transgene were analyzed. We purified AKR1A and studied the activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis. Metabolomic analysis and DNA microarray analysis were performed for a comprehensive study of AKR1A knockout mice. Results: The levels of ascorbic acid in tissues of AKR1A knockout mice were significantly decreased which were completely restored by human AKR1A transgene. The activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis, were suppressed in AKR1A knockout mice. The accumulation of d-glucuronic acid and saccharate in knockout mice tissue and the expression of acute-phase proteins such as serum amyloid A2 are significantly increased in knockout mice liver. Conclusions: AKR1A plays a predominant role in the reduction of both d-glucuronic acid and d-glucurono-γ-lactone in vivo. The knockout of AKR1A in mice results in accumulation of d-glucuronic acid and saccharate as well as a deficiency of ascorbic acid, and also leads to upregulation of acute phase proteins. General significance: AKR1A is a major enzyme that catalyzes the reduction of d-glucuronic acid and d-glucurono-γ-lactone in vivo, besides acting as an aldehyde- detoxification enzyme. Suppression of AKR1A by inhibitors, which are used to prevent diabetic complications, may lead to the accumulation of d-glucuronic acid and saccharate.

Original languageEnglish
Pages (from-to)1787-1796
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1820
Issue number11
DOIs
Publication statusPublished - 2012 Nov

Fingerprint

Aldehyde Reductase
Glucuronic Acid
Knockout Mice
Ascorbic Acid
glucuronolactone reductase
L-glucuronate reductase
Acute-Phase Proteins
Biosynthesis
Lactones
Tissue
Aldehydes
Transgenes
Detoxification
Ascorbic Acid Deficiency
Enzymes
Microarrays
Amyloid
Liver
Metabolomics
Diabetes Complications

Keywords

  • Acute-phase protein
  • Glucose metabolism
  • Oxidoreductase
  • Transgenic rescue

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Takahashi, M., Miyata, S., Fujii, J., Inai, Y., Ueyama, S., Araki, M., ... Kuroki, Y. (2012). In vivo role of aldehyde reductase. Biochimica et Biophysica Acta - General Subjects, 1820(11), 1787-1796. https://doi.org/10.1016/j.bbagen.2012.07.003

In vivo role of aldehyde reductase. / Takahashi, Motoko; Miyata, Satoshi; Fujii, Junichi; Inai, Yoko; Ueyama, Shigemitsu; Araki, Motoko; Soga, Tomoyoshi; Fujinawa, Reiko; Nishitani, Chiaki; Ariki, Shigeru; Shimizu, Takeyuki; Abe, Tomomi; Ihara, Yoshito; Nishikimi, Morimitsu; Kozutsumi, Yasunori; Taniguchi, Naoyuki; Kuroki, Yoshio.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1820, No. 11, 11.2012, p. 1787-1796.

Research output: Contribution to journalArticle

Takahashi, M, Miyata, S, Fujii, J, Inai, Y, Ueyama, S, Araki, M, Soga, T, Fujinawa, R, Nishitani, C, Ariki, S, Shimizu, T, Abe, T, Ihara, Y, Nishikimi, M, Kozutsumi, Y, Taniguchi, N & Kuroki, Y 2012, 'In vivo role of aldehyde reductase', Biochimica et Biophysica Acta - General Subjects, vol. 1820, no. 11, pp. 1787-1796. https://doi.org/10.1016/j.bbagen.2012.07.003
Takahashi M, Miyata S, Fujii J, Inai Y, Ueyama S, Araki M et al. In vivo role of aldehyde reductase. Biochimica et Biophysica Acta - General Subjects. 2012 Nov;1820(11):1787-1796. https://doi.org/10.1016/j.bbagen.2012.07.003
Takahashi, Motoko ; Miyata, Satoshi ; Fujii, Junichi ; Inai, Yoko ; Ueyama, Shigemitsu ; Araki, Motoko ; Soga, Tomoyoshi ; Fujinawa, Reiko ; Nishitani, Chiaki ; Ariki, Shigeru ; Shimizu, Takeyuki ; Abe, Tomomi ; Ihara, Yoshito ; Nishikimi, Morimitsu ; Kozutsumi, Yasunori ; Taniguchi, Naoyuki ; Kuroki, Yoshio. / In vivo role of aldehyde reductase. In: Biochimica et Biophysica Acta - General Subjects. 2012 ; Vol. 1820, No. 11. pp. 1787-1796.
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AU - Araki, Motoko

AU - Soga, Tomoyoshi

AU - Fujinawa, Reiko

AU - Nishitani, Chiaki

AU - Ariki, Shigeru

AU - Shimizu, Takeyuki

AU - Abe, Tomomi

AU - Ihara, Yoshito

AU - Nishikimi, Morimitsu

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