Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.12.7.2 (hydrogenase)
 3,522 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes-induced alterations in heme and hemoproteins, as well as its relationship to drug-mediated induction of ALA Synthase (ALA-S), were examined in female Sprague-Dawley rats. Animals were rendered diabetic by a single i.v. injection of streptozotocin (STZ, 65 mg/kg) and measurements were made at various times after treatment. The basal levels of the key enzymes involved in heme synthesis, ALA-S and ALA-dehydratase (ALA-D), were decreased about 36% and 54%, respectively, 44-46 days after diabetes induction. Furthermore, the catabolism of heme that occurs via microsomal heme oxygenase progressively decreases in activity during the course of diabetes, and reaches 69% of control in 90-day diabetic animals. The basal levels of heme, cytochromes P-450 and b5 were elevated about twofold in diabetic rats as compared with their corresponding control values. The activity of benzo(a)pyrene hydroxylase in diabetic rats was also increased in proportion to the microsomal content of cytochrome P-450. In contrast, delta 4-hydrogenase, the rate-limiting enzyme in corticosterone metabolism, exhibited a 35-65% decrease in activity throughout the experimental period. Tryptophan pyrrolase activity (total, holo-, and apoenzyme) was elevated about 2.5-fold in STZ diabetic rats. In vivo insulin therapy of diabetic animals antagonized the effect of the diabetic state on the above measured parameters. Treatment with aminoglutethimide resulted in about a twofold elevation in ALA-S activity in control as well as chronically diabetic rats. However, a similar stimulatory response in ALA-S activity to CoCl2 administration was observed only in control or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetes-induced metabolic alterations in heme synthesis and degradation and various heme-containing enzymes in female rats. 660 90

Age-related changes in heme and hemoproteins, as well as the effect of testosterone treatment on these modifications were examined in male Sprague-Dawley rats. The activity of delta-aminolevulinic acid synthase (ALA-S) and the microsomal concentration of heme in aged rats were decreased by 37% and 33%, respectively, as compared to young values. In contrast, a marked increase in the activity of microsomal heme oxygenase (MHO) was seen in these animals. In aged rats, the level of cytochrome P-450 was decreased by 37%, as compared to young values. Furthermore, the activities of benzo[a]pyrene hydroxylase and aniline hydroxylase were decreased in proportion to the microsomal content of cytocyrome P-450. Steroid delta 4-hydrogenase, an index of endogenous substrate metabolism, exhibited no changes in activity during the aging process. The level of various hemoproteins such as cytochrome b5 and tryptophan pyrrolase in aged animals remained unaltered despite the decreased hepatic concentration of heme. It is worth noting that testosterone treatment of aged castrated rats restored the level of heme and cytochrome P-450 and the altered enzymatic activities of ALA-S and MHO to the "young" condition. In view of these findings, it is concluded that the events which lead to the low level of heme and cytochrome P-450 and its dependent mixed function oxidase activity during the senescent period could be due to increased rates of MHO and diminished ALA-S activities in these animals.
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PMID:Modification of age-induced changes in heme and hemoproteins by testosterone in male rats. 665 12

Albumin induces oxidative stress and cytokine production in proximal tubular cells (PTECs). Albumin-bound fatty acids (FAs) enhance tubulopathic effects of albumin in vivo. We proposed that FA aggravation of albumin-induced oxidative stress in PTECs might be involved. We hypothesized that mitochondria could be a source of such stress. Using a fluorescent probe, we compared reactive oxygen species (ROS) production after exposure of PTECs to bovine serum albumin (BSA) alone or loaded with oleic acid (OA-BSA) (3-30 g/l for 2 h). There was no difference in cellular albumin uptake, but OA-BSA dose-dependently induced more ROS than BSA alone (P<0.001). OA-BSA-induced ROS was significantly alleviated by mitochondrial inhibition, but not by inhibitors of nicotinamide adenine dinucleotide phosphate hydrogenase (NADPH) oxidase, xanthine oxidase, or nitric oxide synthase. Gene expression analysis showed that neither the NADPH oxidase component p22phox nor xanthine oxidase was induced by BSA or OA-BSA. OA-BSA, in contrast to BSA, failed to induce mitochondrial manganese superoxide dismutase 2 (SOD2) expression. OA-BSA showed a greater capacity than BSA to downregulate heme oxygenase-1 mRNA expression and accentuate inflammatory cytokine mRNA and protein. Supplementation of SOD activity with EUK-8 reduced ROS, and interleukin-6 protein expression was suppressed by both mitochondrial inhibition and SOD augmentation. Thus, in PTECs, FAs accentuate albumin-induced oxidative stress and inflammatory cytokine expression via increased mitochondrial ROS, while frustrating protective antioxidant responses.
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PMID:Albumin-bound fatty acids induce mitochondrial oxidant stress and impair antioxidant responses in proximal tubular cells. 1683 28