Mouse Class 3 Aldehyde Dehydrogenases

Vasiliou, Vasilis; Reuter, Steven F.; Kozak, Christine A.; Nebert, Daniel W.

doi:10.1007/978-1-4615-1965-2_20

Cited by 7 publications

(2 citation statements)

References 21 publications

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“…The latter four genes (the [EpRE] genes) can also be activated through a recognition site in the regulatory region termed the EpRE (also called antioxidant response element), that responds to chemical electrophiles or reactive oxygen (10)(11)(12)(13)(14)(15). The EpRE sequence has been identified in Nmol (41,42), Ahd4 (43,44), Gstal (13,45), and Ugtl*06 (46). These EpREs contain two or more copies of AP-1 or AP-l-like recognition sequences (47).…”

Section: Discussionmentioning

confidence: 99%

Enzyme Induction by L-Buthionine(S,R)-Sulfoximine in Cultured Mouse Hepatoma Cells

Shertzer

Vasiliou²,

Liu³

et al. 1995

Chem. Res. Toxicol.

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Induction of Phase II enzymes of the [Ah] gene battery by L-buthionine (S,R)-sulfoximine (BSO) and other agents was examined in mouse hepatoma Hepa-1c1c7 cells. BSO, a nonelectrophilic inhibitor of gamma-glutamylcysteine synthetase (GCS), is routinely used to examine the toxicological implications of GSH depletion. Exposure to BSO for 24 h produced a 75-85% depletion of GSH levels, proportional to the inhibition of GCS activity, as well as small increases in the UDP-glucuronosyltransferase (UGT, 60%) and glutathione transferase (GST, 30%) enzyme activities in Hepa-1 wild-type (wt) cells. However, for the NAD(P)H:menadione oxidoreductase (NMO1) and cytosolic aldehyde dehydrogenase class 3 (AHD4) enzyme activities, BSO produced larger increases (110% and 170%, respectively). The mechanisms of NMO1 and AHD4 induction were examined further. In Hepa-1 wt cells, NMO1 and AHD4 activities were increased by the aromatic hydrocarbon inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and by the electrophile tert-butylhydroquinone (tBHQ), known inducing agents for these enzymes. However, NMO1 and AHD4 were induced in Ah receptor nuclear translocation-defective mutant (c4) cells by BSO and tBHQ, but not by TCDD, suggesting that the induction by BSO and tBHQ is not Ah receptor-mediated. In wt cells, N-acetylcysteine produced a concentration-dependent increase in intracellular cysteine levels, but not GSH levels, in the absence or presence of BSO. Furthermore, N-acetylcysteine had no effect on NMO1 activity under any conditions examined, suggesting that GSH levels per se, rather than change in overall thiol status, might be mediating increased NMO1 activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Enzyme Induction by L-Buthionine(S,R)-Sulfoximine in Cultured Mouse Hepatoma Cells

Shertzer

Vasiliou²,

Liu³

et al. 1995

Chem. Res. Toxicol.

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“…In addition to being expressed at high concentration in the cornea, it is inducible and constitutively expressed at lower concentrations outside of the cornea, including especially the stomach as well as other ocular and non-ocular tissues (Holmes et al, 1988Algar and Holmes, 1989;Hsu et al, 1992;Lindahl, 1992;Yoshida, 1992;Sladek et al, 1995), where it certainly has an enzymatic function. ALDH3 is a single-copy gene in the mouse (Holmes, 1988;Vasiliou et al, 1993;Vasiliou et al, 1995b), rat (Jones et al, 1988;Hempel and Lindahl, 1989), gray short-tailed opossum (Holmes et al, 1991) and human (Hsu et al, 1992). The marked accumulation of ALDH3 in the transparent cornea suggests that it has more than a strictly enzymatic function in the cornea.…”

Section: Gene Sharing In the Corneamentioning

confidence: 99%

Gene sharing in lens and cornea: facts and implications

Piatigorsky

1998

Progress in Retinal and Eye Research

151

113

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The major water-soluble proteins (crystallins) responsible for the optical properties of the cellular lenses of vertebrates and invertebrates are surprisingly diverse and often differ among species (i.e., are taxon-specific). Many crystallins are encoded by the identical gene specifying a stress protein or a metabolic enzyme which has non-refractive functions in numerous tissues. This double use of a distinct protein has been called gene sharing. Abundant expression of various metabolic enzymes also occurs in a taxon-specific manner in corneal epithelial cells, suggesting that gene sharing extends to this transparent tissue. It has been proposed that one of the most abundant corneal enzymes (aldehyde dehydrogenase class 3) may protect the eye by directly absorbing ultraviolet light, as well as by providing an enzymatic function. It also seems possible that the high expression of corneal enzymes (5-40% of the water-soluble proteins) may reduce scattering in the corneal epithelium by minimizing spatial fluctuations in refractive index as they do in the lens. Thus, gene sharing may be a widespread phenomenon encompassing the lens, cornea and probably other systems. Lens-preferred expression of crystallin genes is integrated in a complex developmental program utilizing in many cases Pax-6. The differential expression of alpha B-crystallin (a small heat shock protein) in different tissues involves the combinatorial use of both shared and lens-specific cis-control elements. Corneal-preferred gene expression appears to depend in part on induction by environmental influences. Among the implications of gene sharing are that gene duplication is not required for the evolution of a new protein phenotype, a change in gene regulation is sufficient, that proteins may be under more than one selective constraint, affecting their evolutionary clock, and that it would be prudent to consider the possibility that any given gene may have important, unrecognized roles when planning to implement gene therapy in the future.

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