Postnatal Development of Mouse Alcohol Dehydrogenases: Agarose Isoelectric Focusing Analyses of the Liver, Kidney, Stomach and Ocular Isozymes

Abstract

The postnatal development of alcohol dehydrogenase (ADH) isozymes was studied in liver, kidney, stomach and eye tissues of C57BL/6J inbred male mice using agarose isoelectric focusing and histochemical methods. Development profiles were tissue specific, with adult patterns being attained by 30 days in the liver and stomach, and by 42 days in the kidneys. Ocular ADH-C₂ increased in activity at the end of the first week, corresponding to the time of eye opening in the neonate.

Development of Aldehyde Dehydrogenase and Alcohol Dehydrogenase in Mouse Eye: Evidence for Light-Induced Changes

“…There were no significant dif ferences (p > 0.05) for this enzyme between animals raised in the dark or light environ ments up to the weaning stage, although by 52 days of age, light-exposed animals showed sig nificantly higher (p < 0 .0 1 ) levels of activity. Agarose-IEF patterns for mouse ocular ADH during development [results not shown] were consistent with previous reports [10,15] that ADH-C2 is the major isozyme throughout. Table 1 illustrates the results for monitor ing possible changes in ocular ALDH and ADH activities for adult male C57BL/6J mice, exposed for a period of 2 months to an alternative environment (total darkness or a regular 12-hour light/dark cycle).…”

“…A major role for agespecific developmental regulation processes is also suggested, given that substantive in creases in ocular ALDH and ADH were ob served in neonatal mice maintained in a dark environment from birth. Moreover, previous developmental studies of male C57BL/6J mouse stomach ADH [15], and ALDH [14], which exhibit predominantly ADH-Co and AHD-4 activities, showed similar develop mental patterns as the ocular isozymes.…”

“…Anterior eye tissues protect UV-sensitive photoreceptor cells of the retina by the direct absorption of UV-B (280-320 nm wavelength range) and UV-A (320-400 nm) light, by the cornea and lens, respectively [4], Recent studies have reported very high levels of ALDH and ADH activities in mammalian cornea [5][6][7], Moreover, biochemical studies, using purified preparations of bovine [8] and baboon [9] ALDHs, have demonstrated that this enzyme is a major soluble protein in mammalian cornea (constituting around 0.5% wet weight of bovine cornea) and may play a dual role in protecting the eye against UV-B light: the oxidation of aldehydes gener ated by light-induced lipid peroxidation, and the direct absorption of UV-B light by corneal ALDH [8], The biochemical genetics of these enzymes has been investigated in the mouse; and for both ALDH and ADH, a stomach iso zyme which is genetically distinct from the liver isozymes has been reported, which shares genetic identity with the corneal en zyme in each case [10]. Mouse stomach ALDH (designated AHD-4) and ADH (ADHCi) have been purified and biochemically characterized and have been shown to prefer medium-chain aliphatic substrates, such as the peroxidic aldehydes [11,12], and are en coded by genes separately localized on the mouse genome: Ahd-4 and Aclh-3 on chromo somes 11 and 3, respectively [10,13], Devel opmental patterns for murine ocular ALDH and ADH isozymes have been recently de scribed using agarose-isoelectric focusing (IEF) methods [14,15], which indicated that AHD-4 and ADH-C2 activities appeared in neonatal animals at around the eye opening stage, and increased further by weaning. This paper reports a quantitative study of ocular ALDH and ADH activity in C57BL/6J inbred mice during neonatal development and pro vides a comparison of mice born and raised in total darkness or under a standard 12-hour light/12-hour darkness environment in order to examine the possible influence of light upon enzyme development.…”

How are children different from adults?

“…Fetal and maternal blood levels of ethanol are equal in pregnant ewes (33). The fetal liver does not express alcohol dehydrogenase until near term (34). Therefore, the majority of ethanol diffuses back across the placenta and is metabolized by the mother.…”

Alcohol misuse and renal damage

“…[63][64][65] Rat kidney tissue contains alcohol dehydrogenase activity that appears to be similar or identical to that of the class I alcohol dehydrogenase in liver. [66][67][68] The oxidation of ethanol by alcohol dehydrogenase generates acetaldehyde which may inhibit the activity of several enzymes, causing the cells to become less efficient. 65,69 In addition, oxidation of acetaldehyde, especially by the acetaldehyde dehydrogenase that has a lower Michaelis-Menten constant, generates species of free radical oxygen that are capable of damaging cell membranes.…”