Cloning, Sequencing, and Enzymatic Activity of an Inducible Aldo-Keto Reductase from Chinese Hamster Ovary Cells

Hyndman, David; Takenoshita, Reiko; Vera, N; Pang, Stephen C.; Flynn, T. Geoffrey

doi:10.1074/jbc.272.20.13286

Cited by 30 publications

(30 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This clone con- (17), and CHO reductase (19), only the amino acid that is different from ARL-1 is shown. For rat Spot 17, only part of the amino acid sequence is available (10).…”

Section: Resultsmentioning

confidence: 99%

Identification and Characterization of a Novel Human Aldose Reductase-like Gene

Cao¹,

Fan²,

Chung³

1998

Journal of Biological Chemistry

269

326

View full text Add to dashboard Cite

We have identified a novel human protein that is highly homologous to aldose reductase (AR). This protein, which we called ARL-1, consists of 316 amino acids, the same size as AR, and its amino acid sequence is 71% identical to that of AR. It is more closely related to the AR-like proteins such as mouse vas deferens protein, fibroblast growth factor-regulated protein, and Chinese hamster ovary reductase, with 81, 82, and 83%, respectively, of its amino acid sequence identical to the amino acid sequence of these proteins. The cDNA of ARL-1 was expressed in Escherichia coli to obtain recombinant protein for characterization of its enzymatic activities. For comparison, the cDNA of human AR was also expressed in E. coli and analyzed in parallel. These two enzymes differ in their pH optima and salt requirement, but they act on a similar spectrum of substrates. Similar to AR, ARL-1 can efficiently reduce aliphatic and aromatic aldehydes, and it is less active on hexoses. While AR mRNA is found in most tissues studied, ARL-1 is primarily expressed in the small intestines and in the colon, with a low level of its mRNA in the liver. The ability of ARL-1 to reduce various aldehydes and the locations of expression of this gene suggest that it may be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs. Interestingly, ARL-1 and AR are overexpressed in some liver cancers, but it is not clear if they contribute to the pathogenesis of this disease. Aldose reductase (AR)1 is a NADPH-dependent enzyme that was first identified by its ability to reduce glucose to sorbitol (1). There are strong indications that it is involved in diabetic complications (2). However, its physiological function is not entirely clear. It is quite abundant in the epithelial cells lining the collecting tubules in the renal medullar. Since hyperosmotic stress can induce the transcription of AR, followed by the accumulation of sorbitol to a level that can affect intracellular osmotic pressure, it was proposed that AR may be involved in the osmoregulation in the kidney (3). In the seminal vesicles, AR may be involved in the production of fructose that is abundant in the semen because sorbitol can be converted to fructose by sorbitol dehydrogenase (1).Besides kidney and testes, AR is present in many other tissues where its function is not clear. Interestingly, glucose is not its preferred substrate (K m ϭ 100 mM, k cat /K m ϭ 2.8 ϫ 10 2 M Ϫ1 min Ϫ1 ) (5). It is more efficient in reducing various aromatic and aliphatic aldehydes including glyceraldehyde, benzaldehyde, pyridine aldehyde etc. (6). In particular, AR's ability to reduce methylglyoxal (K m ϭ 7.8 M, k cat /K m ϭ 1.8 ϫ 10 7 M Ϫ1 min Ϫ1 ) (7), a toxic byproduct of glucose metabolism, and 4-hydroxynonenal (K m ϭ 22 M, k cat /K m ϭ 4.6 ϫ 10 6 M Ϫ1 min Ϫ1 ) (8), a toxic lipid aldehyde produced during oxidative stress, suggests that it may be responsible for detoxifying these and other harmful aldehydes generated by cellular metaboli...

show abstract

“…This clone con- (17), and CHO reductase (19), only the amino acid that is different from ARL-1 is shown. For rat Spot 17, only part of the amino acid sequence is available (10).…”

Section: Resultsmentioning

confidence: 99%

Identification and Characterization of a Novel Human Aldose Reductase-like Gene

Cao¹,

Fan²,

Chung³

1998

Journal of Biological Chemistry

269

326

View full text Add to dashboard Cite

show abstract

“…1) MVDP has a strong preference for NADH; and 2) its enzymatic activity was highly insensitive to most AR inhibitors tested. Based on amino acid sequence identities, MVDP is more homologous to FR-1 (13), CHO reductase (14), ALR1 (15), and human small intestine reductase (16) than to AR (11). The kinetic properties determined for some of these enzymes indicate that they have different enzymatic activities over a range of substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these proteins have been shown to be induced by different factors, including hyperosmotic stress or an excess of galactose (AR) (3,33), growth factors (FR-1) (13), chemical factors (CHO reductase) (14), or hormonal factors (MVDP) (8,9). At present, it is not known whether ALR1 and human small intestine reductase, the human homologs, are also inducible.…”

Section: Discussionmentioning

confidence: 99%

“…MVDP shares ϳ70% amino acid identity with human, rabbit, rat, and mouse ARs (10,11), and MVDP gene structure is similar to that of the human AR gene (12). However, MVDP is more closely related to the mouse fibroblast growth factor-regulated protein FR-1 (13), Chinese hamster ovary reductase (14), the human AR-like gene ALR1 (15), and human small intestine reductase (16). These proteins share ϳ80 -90% sequence identities and form a distinct subgroup within the AKR1B group according to the new nomenclature proposed by Jez et al (17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Product of Side-chain Cleavage of Cholesterol, Isocaproaldehyde, Is an Endogenous Specific Substrate of Mouse Vas Deferens Protein, an Aldose Reductase-like Protein in Adrenocortical Cells

Lefrançois‐Martinez¹,

Tournaire²,

Martinez³

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

Mouse vas deferens protein (MVDP) is an aldose reductase-like protein that is highly expressed in the vas deferens and adrenal glands and whose physiological functions were unknown. We hereby describe the enzymatic characteristics of MVDP and its role in murine adrenocortical Y1 cells. The murine aldose reductase (AR) and MVDP cDNAs were expressed in bacteria to obtain recombinant proteins and to compare their enzymatic activities. Recombinant MVDP was functional and displayed kinetic properties distinct from those of murine AR toward various substrates, a preference for NADH, and insensitivity to AR inhibitors. For MVDP, isocaproaldehyde, a product of side-chain cleavage of cholesterol generated during steroidogenesis, is the best natural substrate identified so far. In Y1 cells, we found that NADH-linked isocaproaldehyde reductase (ICR) activity was much higher than NADPH-linked ICR activity and was not abolished by AR inhibitors. We demonstrate that in Y1 cells, forskolin-induced MVDP expression enhanced NADH-linked ICR activity by 5-6-fold, whereas no variation in ICR-linked NADPH activity was observed in the same experiment. In cells stably transfected with MVDP antisense cDNA, NADH-linked ICR activity was abolished even in the presence of forskolin, and the isocaproaldehyde toxicity was increased compared with that of intact Y1 cells, as measured by isocaproaldehyde LD 50 . In Y1 cells transfected with MVDP antisense cDNA, forskolin-induced toxicity was abolished by aminoglutethimide. These results indicate that in adrenocortical cells, MVDP is responsible for detoxifying isocaproaldehyde generated by steroidogenesis.

show abstract

“…During hepatocarcinogenesis, the most prominent tumourassociated protein variant (spot 17) revealed a 92% identity with MVDP (Zeindl-Eberhart et al 1994). An inducible aldo-keto reductase from CHO cells shows greatest amino acid sequence identity to mouse FR-1 and MVDP (92 and 80% respectively) (Hyndman et al 1997). Although aldose reductases and other members of the aldo-keto reductase family are involved in cellular homeostasis (Bhatnagar & Srivastava 1992), little is known about the signal transduction pathways that mediate the response of these genes to extracellular signalling molecules.…”

Section: Introductionmentioning

confidence: 99%

Cyclic AMP regulates expression of the gene coding for a mouse vas deferens protein related to the aldo-keto reductase superfamily in human and murine adrenocortical cells

Aigueperse

Martinez²,

Lefrançois‐Martinez³

et al. 1999

Journal of Endocrinology

View full text Add to dashboard Cite

Mouse vas deferens protein (MVDP) is a member of the aldo-keto reductase superfamily. The regulation of MVDP gene expression by activators of the protein kinase A signalling pathway was investigated in human (H295-R) and murine (Y1) adrenocortical carcinoma cells. Immunoblotting with polyclonal antibodies showed that MVDP is expressed in adrenal glands from mouse, rat, rabbit and guinea-pig, probably under the control of ACTH. In both adrenocortical cell lines used, MVDP is constitutively synthesized and its accumulation is increased by treatment with cAMP or forskolin. MVDP mRNA steady-state levels were up-regulated by forskolin in adrenocortical cells by a process that does not require de novo protein synthesis. The results suggest that cAMP is at least one of the key regulators of adrenal MVDP expression and that this effect is direct.

show abstract

Cloning, Sequencing, and Enzymatic Activity of an Inducible Aldo-Keto Reductase from Chinese Hamster Ovary Cells

Cited by 30 publications

References 34 publications

Identification and Characterization of a Novel Human Aldose Reductase-like Gene

Identification and Characterization of a Novel Human Aldose Reductase-like Gene

Product of Side-chain Cleavage of Cholesterol, Isocaproaldehyde, Is an Endogenous Specific Substrate of Mouse Vas Deferens Protein, an Aldose Reductase-like Protein in Adrenocortical Cells

Cyclic AMP regulates expression of the gene coding for a mouse vas deferens protein related to the aldo-keto reductase superfamily in human and murine adrenocortical cells

Contact Info

Product

Resources

About