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Expression Pattern, Ethanol-Metabolizing Activities, and Cellular Localization of Alcohol and Aldehyde Dehydrogenases in Human Pancreas: Implications for Pathogenesis of Alcohol-Induced Pancreatic Injury

Authors

  • Chien-Ping Chiang,

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • Chew-Wun Wu,

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • Shiao-Pieng Lee,

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • Chia-Chi Chung,

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • Chi-Wei Wang,

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • Shou-Lun Lee,

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • Shin Nieh,

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • Shih-Jiun Yin

    1. From the Graduate Institute of Medical Sciences (C-PC) and Department of Biochemistry (C-CC, C-WW, S-JY), National Defense Medical Center, Taipei; Departments of Dermatology (C-PC), Dentistry (S-PL) and Pathology (SN), Tri-Service General Hospital, Taipei; Department of Surgery, Taipei Veterans General Hospital (C-WW), Taipei; Department of Biological Science and Technology, China Medical University (S-LL), Taichung, Taiwan.
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  • This work was supported by grants from the National Science Council 81-0412-B016-539Y/96-2320-B016-018-MY3 (S-JY) and the National Health Research Institutes GT-EX89-B939P (S-JY).

Reprint requests: Shih-Jiun Yin, Department of Biochemistry, National Defense Medical Center, 161 Minchuan East Road Section 6, Taipei 11453, Taiwan; Tel.: 886-2-87923100 ext 18800; Fax: 886-2-87924818; E-mail: yinsj@ndmc.idv.tw

Abstract

Background:  Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are major enzymes responsible for metabolism of ethanol. Genetic polymorphisms of ADH1B, ADH1C, and ALDH2 occur among racial populations. The metabolic effect and metabolites contribute to pathogenesis of pancreatic injury. The goal of this study was to determine the functional expressions and cellular localization of ADH and ALDH families in human pancreas.

Methods:  Fifty five surgical specimens of normal pancreas as well as 15 samples each for chronic pancreatitis and pancreatic cancer from archival formalin-fixed paraffin-embedded tissue specimens were investigated. Class-specific antibodies were prepared by affinity chromatographies from rabbit antisera raised against recombinant human ADH1C1, ADH4, ADH5, ADH7, ALDH1A1, ALDH2, and ALDH3A1. The isozyme expression patterns of ADH/ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting, and the cellular localizations were detected by immunohistochemistry and histochemistry.

Results:  At 33 mM ethanol, pH 7.5, the activities were significantly different between allelic phenotypes of ADH1B. The activity of ALDH2-inactive phenotypes was slightly lower than ALDH2-active phenotypes at 200 μM acetaldehyde. The protein contents were in the following decreasing order: ALDH1A1, ALDH2, ADH1, and ADH5. ADH1B was detected in the acinar cells and ADH1C in the ductular, islet, and stellate cells. The expression of ADH1C appeared to be increased in the activated pancreatic stellate cells in chronic pancreatitis and pancreatic cancer.

Conclusions:  Alcohol dehydrogenase and ALDH family members are differentially expressed in the various cell types of pancreas. ADH1C may play an important role in modulation of activation of pancreatic stellate cells.

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