Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.3 (HSD)
 3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While studying the bile acid synthetic pathway of hamsters, we discovered an NADP+-dependent liver microsomal 7alpha-hydroxycholesterol dehydrogenase (7alpha-HCD) activity that was not observed in rat liver microsomal fractions. The hamster liver microsomal 7alpha-HCD was purified to homogeneity using 2', 5'-ADP and cholic acid-agarose affinity chromatography. 7alpha-HCD displayed a molecular weight of approximately 34,000 on SDS-polyacrylamide gel electrophoresis; it is an intrinsic membrane protein of the hamster liver endoplasmic reticulum and exists as a multimeric aggregate in pure form. Partial N-terminal amino acid sequence analysis showed that 7alpha-HCD had high sequence similarity to human 11beta-hydroxysteroid dehydrogenase (11beta-HSD; 24/30 amino acid identity). The Km values for corticosterone and 7alpha-hydroxycholesterol were 1.2 and 1.9 microM, respectively, for purified 7alpha-HCD; both reactions displayed identical Vmax values (approximately 170 nmol/min/mg of protein). The IC50 of carbenoxolone, a competitive inhibitor of 11beta-HSD, was 75 nM for 7alpha-hydroxycholesterol dehydrogenation and 210 nM for corticosterone dehydrogenation. The tissue-specific expression in hamster was as follows: adrenal >/= liver > kidney > testis >> brain > lung. Microsomal 7alpha-HCD is uniquely expressed in hamster liver and to some extent in human liver but not in rat liver. Western blot analysis with two antibodies elicited against an N-terminal peptide of the human 11beta-HSD and purified hamster liver 7alpha-HCD, respectively, suggested the presence of multiple forms of 7alpha-HCD in hamster liver, most likely due to the existence of a family of 11beta-HSD proteins. Since 7-oxocholesterol is a potent inhibitor of cholesterol 7alpha-hydroxylase, alternative mechanisms for regulation of bile acid synthesis may exist in human and hamster liver due to production of this metabolite and its potential as an oxysterol.
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PMID:Purification and characterization of hamster liver microsomal 7alpha-hydroxycholesterol dehydrogenase. Similarity to type I 11beta-hydroxysteroid dehydrogenase. 963 80

Although the effect of NaCl on serum lipid levels and hypertension is well known, the detailed mechanism of lipoprotein metabolism still remains unclear. To study the physiological effects of high salt consumption on lipoprotein metabolism, NaCl was administered to human cells and zebrafish. Wildtype zebrafish (10-week old) were fed 10% NaCl (wt/wt) in tetrabit diet with or without 4% cholesterol (wt/wt) for 21 weeks. Treatment with NaCl accelerated oxidation and glycation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) as well as induced proteolytic degradation and aggregation. NaCl treatment also exacerbated phagocytosis of oxLDL into macrophage as well as cytotoxicity. The consumption of high salt diet (HSD, final 5% or 10% in diet, wt/wt) supplemented with or without 4% cholesterol for 21 weeks resulted in a remarkable elevation of serum cholesterol, triglyceride, glucose, and hepatic inflammation levels in zebrafish with significant weight loss. Fertility based on egg production was reduced by up to 45% in the HSD group. However, embryonic survivability after hatching was significantly lowered to less than 55%, whereas the control group showed 87% survival. The HSD group showed abnormal testicular histology as well as spermatogenic defects, especially upon the consumption of HCD. These results suggest that hyperlipidemia and high salt consumption have an additive effect on male fertility impairment. High salt consumption exacerbates hyperlipidemia, inflammation, spermatogenic defects, and infertility via a modification of lipoproteins.
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PMID:High-dose consumption of NaCl resulted in severe degradation of lipoproteins associated with hyperlipidemia, hyperglycemia, and infertility via impairment of testicular spermatogenesis. 3009 Mar 70