The Functional Implications of Acetaldehyde Binding to Cell Constituentsa

Sorrell, Michael F.; Tuma, Dean J.

doi:10.1111/j.1749-6632.1987.tb48652.x

Cited by 78 publications

(24 citation statements)

References 41 publications

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“…How ethanol might alter rab2 distribution and function is undefined, although it is well documented that ethanol inhibits the activity of a variety of cellular enzymes (42), including membrane-associated and soluble glycosyltransferases (43,44), hepatic galactosyltransferase (14), and yeast glucose-6-phosphate dehydrogenase (45). A particularly relevant future line of investigation will determine whether rab proteins, including rab2 and rab6, contain reactive lysine residues available to form stable acetaldehyde-protein adducts (42).…”

Section: Discussionmentioning

confidence: 99%

“…A particularly relevant future line of investigation will determine whether rab proteins, including rab2 and rab6, contain reactive lysine residues available to form stable acetaldehyde-protein adducts (42). If these lysine residues are located within biologically active regions of rab proteins (i.e., GTP binding domains, effector domain), adduct formation might be expected to have profound functional consequences on secretion.…”

Section: Discussionmentioning

confidence: 99%

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Ethanol-induced retention of nascent proteins in rat hepatocytes is accompanied by altered distribution of the small GTP-binding protein rab2.

Larkin¹,

Oswald²,

McNiven³

1996

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ethanol-induced retention of nascent proteins in rat hepatocytes is accompanied by altered distribution of the small GTP-binding protein rab2.

Larkin¹,

Oswald²,

McNiven³

1996

J. Clin. Invest.

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“…Previous in vitro studies have demonstrated the formation of acetaldehyde adducts with several hepatic proteins and cell constituents (2)(3)(4)(5)(6)(7)(8). Acetaldehyde derived from oxidation of ['4C]ethanol by rat liver slices has also been shown to bind to preformed hepatocyte proteins (28).…”

Section: Discussionmentioning

confidence: 99%

“…Earlier studies have indicated that acetaldehyde selectively modifies the epsilon amino groups oflysine residues (43) yielding immunogenic derivatives upon stabilization with appropriate reducing agents (13,44,45). Reaction of acetaldehyde with proteins may, however, also involve other amino acid residues including cysteine, valine and tyrosine (1,5,46), and other types of adducts of which at least the acetaldehyde-tyrosine linkage, possibly involving a cyclic imidazolidinone, has been shown to be immunoreactive (20,46). At this time we also cannot rule out the possibility that the antibodies would recognize other types of arrangements, such as cross-linking, which is known to occur in reactions with aldehydes and cellular components (47,48).…”

Section: I5amentioning

confidence: 99%

Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption.

Niemelä¹,

Juvonen²,

Parkkila³

1991

J. Clin. Invest.

145

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Acetaldehyde, the toxic product of ethanol metabolism in the liver, covalently binds to a variety of proteins. Recent studies indicate that such binding can stimulate the production of antibodies against the acetaldehyde adducts. We raised rabbit antibodies which recognized various protein-acetaldehyde conjugates but not the corresponding control proteins. Such antibodies were used in immunohistochemical studies to find out whether acetaldehyde-generated epitopes can be detected from liver specimens of 13 human subjects with different degrees of alcohol consumption. While the specimens obtained from alcohol abusers (n = 4) and alcoholics (n = 3) exhibited marked positive staining for acetaldehyde adducts inside the hepatocytes in a granular uneven pattern, the control samples (n = 6) were almost devoid of immunoreactivity. In the alcohol abusers with an early stage of alcohol-induced liver damage, staining was detected exclusively around the central veins.The data indicate that intracellular acetaldehyde adducts occur in the centrilobular region of the liver of individuals consuming excessive amounts of alcohol. Immunohistochemical detection of such adducts may prove to be of value in the early identification of alcohol abuse and in elucidating the mechanisms of alcohol-induced organ damage. (J. Clin. Invest. 1990.

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“…[1][2][3] Various reactive aldehydic products including AA and the oxidant products, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), may be generated in vivo as a result of alcohol consumption. These metabolic products can bind to exposed proteins and cellular constituents forming stable adducts.…”

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confidence: 99%

Induction of cytochrome P450 enzymes and generation of protein-aldehyde adducts are associated with sex-dependent sensitivity to alcohol-induced liver disease in micropigs

et al. 1999

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To assess possible links between ethanol-induced oxidant stress, expression of hepatic cytochrome P450 (CYP) enzymes, and sex steroid status, we used immunohistochemical methods to compare the generation of protein adducts of acetaldehyde (AA), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) with the amounts of CYP2E1, CYP2A, and CYP3A in the livers of castrated and noncastrated male micropigs fed ethanol for 12 months. In castrated micropigs, ethanol feeding resulted in accumulation of fat, hepatocellular necrosis, inflammation, and centrilobular fibrosis, whereas only minimal histopathology was observed in their noncastrated counterparts. CYP2A and CYP3A were more prominent in the castrated animals than in the noncastrated micropigs. Ethanol feeding increased the hepatic content of all CYP forms. The most significant increases occurred in CYP2E1 and CYP3A in the noncastrated animals and in CYP2E1 and CYP2A in the castrated animals. Ethanol-fed castrated animals also showed the greatest abundance of perivenular adducts of AA, MDA, and HNE. In the noncastrated ethanol-fed micropigs a low expression of each CYP form was associated with scant evidence of aldehyde-protein adducts. Significant correlations emerged between the levels of different CYP forms, protein adducts, and plasma levels of sex steroids. The present findings indicate that the generation of proteinaldehyde adducts is associated with the induction of several cytochrome enzymes in a sex steroid-dependent manner. It appears that the premature, juvenile, metabolic phenotype, as induced by castration, favors liver damage. The present findings should be implicated in studies on the gender differences on the adverse effects of ethanol in the liver.

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The Functional Implications of Acetaldehyde Binding to Cell Constituentsa

Cited by 78 publications

References 41 publications

Ethanol-induced retention of nascent proteins in rat hepatocytes is accompanied by altered distribution of the small GTP-binding protein rab2.

Ethanol-induced retention of nascent proteins in rat hepatocytes is accompanied by altered distribution of the small GTP-binding protein rab2.

Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption.

Induction of cytochrome P450 enzymes and generation of protein-aldehyde adducts are associated with sex-dependent sensitivity to alcohol-induced liver disease in micropigs

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