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

Chiang, Chien-Ping; Wu, Chew-Wun; Lee, Shiao-Pieng; Chung, Chia-Chi; Wang, Chi-Wei; Lee, Shou-Lun; Nieh, Shin; Yin, Shih‐Jiun

doi:10.1111/j.1530-0277.2009.00927.x

Cited by 32 publications

(26 citation statements)

References 47 publications

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“…The expression of recombinant enzymes in Escherichia coli and purification to apparent homogeneity for human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, ADH3, ADH4, and for human ALDH1A1, ALDH2, ALDH3A1 were carried out as described previously [6,15,29]. All of the isolated recombinant enzyme forms exhibited a single coomassie blue-staining protein band with molecular masses of 40 kDa, 55 kDa, and 54 kDa for ADHs, ALDH1A1/2, and ALDH3A1, respectively, on SDS-polyacrylamide gel electrophoresis.…”

Section: Expression and Purification Of Human Adh And Aldhmentioning

confidence: 99%

Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: Assessment of the effects on first-pass metabolism of ethanol

Lee

et al. 2015

Biochemical Pharmacology

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Section: Expression and Purification Of Human Adh And Aldhmentioning

confidence: 99%

Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: Assessment of the effects on first-pass metabolism of ethanol

Lee

et al. 2015

Biochemical Pharmacology

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“…Thus, pancreatic stellate cells are intimately involved in the regulation of both physiologic, as well as pathologic aspects of the pancreas [64,65] . Both rat and human pancreatic stellate cells express ADH [66,67] . Furthermore, ADH activity is up regulated in pancreatic stellate cells of individuals suffering from chronic pancreatitis and pancreatic cancer [67] .…”

Section: Involvement Of Pancreatic Stellate Cells In Alcoholic Pancrementioning

confidence: 99%

“…Both rat and human pancreatic stellate cells express ADH [66,67] . Furthermore, ADH activity is up regulated in pancreatic stellate cells of individuals suffering from chronic pancreatitis and pancreatic cancer [67] . The fact that pancreatic stellate cells express ADH indicates that these cells can produce acetaldehyde when exposed to ethanol.…”

Section: Involvement Of Pancreatic Stellate Cells In Alcoholic Pancrementioning

confidence: 99%

Alcoholic pancreatitis: New insights into the pathogenesis and treatment

Clemens

Schneider

Arkfeld

et al. 2016

WJGP

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Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis. Core tip: There is currently no specific pharmacotherapy for pancreatitis. Although ethanol abuse is commonly associated with both acute and chronic pancreatitis, ethanol does not itself cause pancreatitis. Instead it appears that ethanol and its metabolic by-products sensitize the pancreas to damage from other factors. Detailed understanding of the mechanisms by which ethanol sensitizes the pancreas to damage has identified a number of promising targets for therapy. It is hoped that further preclinical and clinical studies will lead to the development of successful treatment of both acute and chronic pancreatitis. REVIEWClemens DL, Schneider KJ, Arkfeld CK, Grode JR, Wells MA, Singh S. Alcoholic pancreatitis: New insights into the pathogenesis and treatment.

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“…The ALDH activity in the pancreas is nearly fivefold lower than that of the liver, contributing in this way to acetaldehyde glandular accumulation [110]. Despite this fact, data from animal studies have shown that acetaldehyde by itself does not elicit directly acute pancreatitis [111,112].…”

Section: Harmful Effects Of Acetaldehyde and Fatty Acid Ethyl Esters mentioning

confidence: 95%

Nonalcoholic fatty pancreas disease as an endogenous alcoholic fatty pancreas disease

Medeiros¹,

Lima²

2016

Gastroenterol Hepatol Endosc

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Nonalcoholic fatty pancreas disease (NAFPD) is closely linked to nonalcoholic steatohepatitis (NASH), suggesting that the two conditions share a common etiopathogenetic background. In Addition, growing evidence indicates that endogenous ethanol (EE) plays a fundamental role in NASH pathogenesis. Accordingly, it is intuitively appealing to assume that EE plays also a causative role in NAFPD development. This connection is further supported by the finding that NAFPD shares with alcoholic fatty pancreas disease (AFPD) similar metabolic signaling pathways and histopathological features. However, low blood alcohol concentrations (BAC) along with the alleged inability of gut microbiota to produce toxic amounts of ethanol are the main obstacles to validate the idea of an endogenous alcoholic fatty pancreas disease (EAFPD). Here, we provide a mechanistic explanation reconciling the EAFPD hypothesis with these apparently conflicting observations. The key conclusions of our investigation are as follows. First, ethanol is a prodrug, implicating that under extensive presystemic metabolism BACs can be low and/ or absent. Second, oro-gastrointestinal microbiota may produce higher amounts of ethanol than those required to cause AFPD. Last, livers of NASH/NAFPD individuals overexpress all genes encoding alcohol-metabolizing enzymes identically to livers of patients with alcoholic hepatitis. Even more importantly, the upregulation of these genes is higher in the early steatotic stage of nonalcoholic fatty liver disease than in alcoholic hepatitis. This suggests a greater exposure of the liver, and by extension, of the pancreas, to ethanol in the former than in the latter condition. In summary, this paper provides a mechanistic framework for how NAFPD indeed may be an EAFPD.

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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

Abstract: 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.

Cited by 32 publications

References 47 publications

Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: Assessment of the effects on first-pass metabolism of ethanol

Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: Assessment of the effects on first-pass metabolism of ethanol

Alcoholic pancreatitis: New insights into the pathogenesis and treatment

Nonalcoholic fatty pancreas disease as an endogenous alcoholic fatty pancreas disease

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