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DHRS4  -  dehydrogenase/reductase (SDR family) member 4

Homo sapiens

Synonyms: CR, Dehydrogenase/reductase SDR family member 4, FLJ11008, NADPH-dependent carbonyl reductase/NADP-retinol dehydrogenase, NADPH-dependent retinol dehydrogenase/reductase, ...
 
 
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Disease relevance of DHRS4

 

High impact information on DHRS4

  • We have previously isolated two types of CR/20beta-HSD cDNAs from ovarian follicle of rainbow trout (Oncorhynchus mykiss) [1].
  • Carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase (CR/20beta-HSD) is an enzyme that converts 17alpha-hydroxyprogesterone to 17alpha, 20beta-dihydroxy-4-pregnen-3-one (the maturation-inducing hormone of salmonid fish) [1].
  • After adjustment for age, central and total prostate volumes were significantly smaller, and plasma prostate-specific antigen and 5alpha-dihydrotestosterone (DHT) concentrations and International Prostate Syndrome Scores were significantly lower, in CR compared with either ACM or AR, whereas the scores of the latter two groups were similar [5].
  • The present study sought to determine whether carbonyl reductase (CR) catalyzes reduction of 4ONE, representing a potential pathway for metabolism of the lipid peroxidation product [6].
  • CR supplementation did not affect food intake, body weight, nutritional parameters and IL-6 levels in non-tumor-bearing mice [4].
 

Chemical compound and disease context of DHRS4

  • To compare the effects of captopril with more conventional drugs on proteinuria and progression of renal disease, we conducted a prospective, 18-month study in 42 proteinuric (> 500 mg/day) NIDDM and, for comparison, in 31 nondiabetic patients with a variety of renal diseases (NDRD) [7].
  • 3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) from Comamonas testosteroni is a key enzyme involved in the degradation of steroids and xenobiotic carbonyl compounds [8].
 

Biological context of DHRS4

  • This mode of dimerization is, however, sterically impossible in 3alpha-HSD/CR because of a 28 amino acids insertion into the classical Rossmann-fold motif between strand betaE and helix alphaF [9].
  • The aim of this work is to study the temporary variation of oxidative stress in renal transplants, both in plasma and in erythrocytes (CR) [10].
 

Anatomical context of DHRS4

  • We evaluated nutritional parameters such as serum glucose level and wasting of adipose tissue and muscle in tumor-bearing and non-tumor-bearing mice treated with C. rhizoma (CR) supplement or a normal diet [4].
  • RESULTS: In comparison to totally untreated rats the testosterone treatment increased weight of prostates and seminal vesicles 3-5-fold and this proliferation was largely and equipotently inhibited by finasteride and CR BNO 1055 [11].
  • Aldo-keto reductases (AKRs) and carbonyl reductase (CR, EC 1.1.1.184) purified from human liver cytosol were incubated with varying substrate concentrations and 6beta-naltrexol or reduced dolasetron were analysed by HPLC [12].
  • In an attempt to improve the prognosis of 20 patients with poor-risk advanced-stage HD, we evaluated the role of early high-dose therapy (HDT) and autologous bone marrow/stem cell transplantation (ASCT) during the first complete or partial remission (CR/PR) [13].
 

Associations of DHRS4 with chemical compounds

  • Poly(uridylic acid) has a broad band at approximately 1695 cm-1, predominantly C2 carbonyl stretch, an unresolved CR carbonyl band (probably near 1660 cm-1), and a ring vibration at approximately 1636 cm-1 [14].
  • Eighteen NDRD patients received captopril, and 13 received conventional drugs [7].
  • METHODS: Immature 24-day-old male rats were fed with testosterone (T)-containing food and injected with 30mg CR BNO 1055 or 0.5mg finasteride for 5 days [11].
  • Multivariate analysis on patients receiving the COPP chemotherapy revealed that the independent prognostic variables significantly determining CR rate and survival included clinical stage (p = 0.04) and serum lactate dehydrogenase level (p = 0.001) [15].
  • Treatment-related variables associated with higher CNS-relapse rates (34-50%) were: delay of > or = 14 days from diagnosis to first i.t. injection, < 5 i.t. treatments, delay of i.t. prophylaxis until after attaining CR and systemic treatment lacking high-dose methotrexate +/- ara-C (each P < or = 0.17) [16].
 

Analytical, diagnostic and therapeutic context of DHRS4

  • To investigate the structure/function relationships of CR/20beta-HSDs, we generated mutants by site-directed mutagenesis at the following positions: MutA/I15T, MutB/T15I, and MutB/Q27K [1].
  • A catalytic triad of Ser-114, Tyr-155, and Lys-159 in 3alpha-HSD/CR has been proposed based on structural analysis and sequence alignment of the short chain dehydrogenase/reductase family [3].
  • The response to chemotherapy was grouped as specified as complete (CR), partial response (PR), no change (NC), and progressive disease (PD), according to the change in tumor size on chest roentgenography and CT [17].
  • When the data from these women were related to weight or Quetelet's Index (QI = wt/ht2) by unweighted linear regression, the only values that were significantly correlated with weight and QI were [rho]T,E2BM and [rho]A,E1BM; for all other [rho] and CR values there was no correlation with weight or QI [18].
  • Crystallization and structure analysis showed that 3alpha-HSD/CR is active as a dimer [9].

References

  1. Isoleucine-15 of rainbow trout carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase is critical for coenzyme (NADPH) binding. Guan, G., Todo, T., Tanaka, M., Young, G., Nagahama, Y. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with a high-dose doxorubicin-containing regimen. Zuckerman, K.S., LoBuglio, A.F., Reeves, J.A. J. Clin. Oncol. (1990) [Pubmed]
  3. Mechanistic roles of Ser-114, Tyr-155, and Lys-159 in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni. Hwang, C.C., Chang, Y.H., Hsu, C.N., Hsu, H.H., Li, C.W., Pon, H.I. J. Biol. Chem. (2005) [Pubmed]
  4. Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma. Iizuka, N., Hazama, S., Yoshimura, K., Yoshino, S., Tangoku, A., Miyamoto, K., Okita, K., Oka, M. Int. J. Cancer (2002) [Pubmed]
  5. Ethnicity and migration as determinants of human prostate size. Jin, B., Turner, L., Zhou, Z., Zhou, E.L., Handelsman, D.J. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  6. Human carbonyl reductase catalyzes reduction of 4-oxonon-2-enal. Doorn, J.A., Maser, E., Blum, A., Claffey, D.J., Petersen, D.R. Biochemistry (2004) [Pubmed]
  7. Effect of long-term therapy with captopril on proteinuria and renal function in patients with non-insulin-dependent diabetes and with non-diabetic renal diseases. Liou, H.H., Huang, T.P., Campese, V.M. Nephron (1995) [Pubmed]
  8. Characterization and recombinant expression of the translational repressor RepB of 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase in Comamonas testosteroni. Xiong, G., Martin, H.J., Maser, E. Chem. Biol. Interact. (2003) [Pubmed]
  9. Understanding oligomerization in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni: An in silico approach and evidence for an active protein. Hoffmann, F., Sotriffer, C., Evers, A., Xiong, G., Maser, E. J. Biotechnol. (2007) [Pubmed]
  10. Glutathione determination and a study of the activity of glutathione-peroxidase, glutathione-transferase, and glutathione-reductase in renal transplants. De Vega, L., Férnandez, R.P., Mateo, M.C., Bustamante, J.B., Herrero, A.M., Munguira, E.B. Renal failure. (2002) [Pubmed]
  11. Inhibition of 5alpha-reductase in the rat prostate by Cimicifuga racemosa. Seidlov??-Wuttke, D., Pitzel, L., Thelen, P., Wuttke, W. Maturitas (2006) [Pubmed]
  12. Carbonyl reduction of naltrexone and dolasetron by oxidoreductases isolated from human liver cytosol. Breyer-Pfaff, U., Nill, K. J. Pharm. Pharmacol. (2004) [Pubmed]
  13. High-dose chemo/radiotherapy and autologous bone marrow or stem cell transplantation for poor-risk advanced-stage Hodgkin's disease during first partial or complete remission. Nademanee, A., Molina, A., Fung, H., Stein, A., Parker, P., Planas, I., O'Donnell, M.R., Snyder, D.S., Kashyap, A., Spielberger, R., Bhatia, R., Krishnan, A., Sniecinski, I., Vora, N., Slovak, M., Dagis, A., Niland, J.C., Forman, S.J. Biol. Blood Marrow Transplant. (1999) [Pubmed]
  14. Infrared spectroscopy of polynucleotides in the carbonyl region in H2O solution: A.U systems. Miles, H.T., Frazier, J. Biochemistry (1978) [Pubmed]
  15. COPP chemotherapy for elderly patients with intermediate and high grade non-Hodgkin's lymphoma. Liang, R., Todd, D., Chan, T.K., Chiu, E., Lie, A., Ho, F. Hematological oncology. (1993) [Pubmed]
  16. Intrathecal chemotherapy alone is inadequate central nervous system prophylaxis in patients with intermediate-grade non-Hodgkin's lymphoma. Chua, S.L., Seymour, J.F., Streater, J., Wolf, M.M., Januszewicz, E.H., Prince, H.M. Leuk. Lymphoma (2002) [Pubmed]
  17. Comparison of Tc-99m sestamibi, serum neuron-specific enolase and lactate dehydrogenase as predictors of response to chemotherapy in small cell lung cancer. Lim, S.C., Park, K.O., Kim, Y.C., Na, K.J., Song, H., Bom, H.S. Cancer Biother. Radiopharm. (2000) [Pubmed]
  18. Androgen and estrogen metabolism: relationship to obesity. Longcope, C., Baker, R., Johnston, C.C. Metab. Clin. Exp. (1986) [Pubmed]
 
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