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1.
Ochratoxin A, a nephrotoxin produced as a secondary metabolite by A. ochraceus, is a potent inhibitor of renal PEPCK activity, in vivo. When fed orally to rats for 2 days, renal PEPCK activity is reduced 50% by a total dose of 0.3-0.5 mg toxin. Renal gluconeogenic capacity is reduced only after PEPCK activity is inhibited by 50%. Hepatic PEPCK activity is unaffected up to 1.5-2.0 mg ochratoxin A, which were the highest doses tested. Other enzymes located in proximal convoluted tubules, including phosphatedependent glutaminase, γ-glutamyl transpeptidase, pyruvate carboxylase, and Na,K-ATPase, are not affected. Renal protein synthesis from [3H]phenylalanine or [3H]leucine is inhibited 30–40% by ochratoxin A in vivo. By covalently coupling the toxin to albumin with carbodiimide or mixed anhydride, the inhibitory effect on renal PEPCK activity is retained, but protein synthesis is not affected and cytological evidence of nephrotoxicity is lost. Injection of the ochratoxin A-albumin carbodiimide complex results in a decrease of hepatic PEPCK activity as well. Removal of the phenylalanine group from the toxin prevents the in vivo inhibition of PEPCK activity, as well as protein synthesis. We conclude that the decrease in renal PEPCK activity, in vivo, requires the phenylalanine group of ochratoxin A, and occurs by a mechanism independent of the known nephrotoxicity effects. 相似文献
2.
Regulation of transferrin receptor cycling by protein kinase C is independent of receptor phosphorylation at serine 24 in Swiss 3T3 fibroblasts 总被引:6,自引:0,他引:6
Treatment of Swiss 3T3 fibroblasts with tumor-promoting phorbol diester or with platelet-derived growth factor caused the phosphorylation of the transferrin receptor by protein kinase C (Ca2+/phospholipid-dependent enzyme) at serine 24 and increased the cell surface expression of the transferrin receptor. The hypothesis that the regulation of transferrin receptor cycling by protein kinase C is causally related to the phosphorylation of the receptor at serine 24 was critically tested. Site-directed mutagenesis of the human transferrin receptor cDNA was used to substitute serine 24 with threonine or alanine residues in order to create phosphorylation defective receptors. Wild-type and mutated transferrin receptors were expressed in Swiss 3T3 fibroblasts using the retrovirus vector pZipNeoSV (X). These receptors were functionally active and caused the receptor-mediated endocytosis of diferric transferrin. Incubation of the fibroblasts with phorbol diester caused the phosphorylation of the wild-type (Ser-24) human transferrin receptor, but this treatment did not result in the phosphorylation of the mutated (Ala-24 and Thr-24) receptors. The cycling of the phosphorylation defective receptors was regulated by phorbol diester and platelet-derived growth factor in a manner similar to that observed for the wild-type receptor. We conclude that the regulation of transferrin receptor cycling by protein kinase C is independent of receptor phosphorylation at serine 24 in Swiss 3T3 fibroblasts. 相似文献
3.
Molecular cloning of the human casein kinase II alpha subunit 总被引:12,自引:0,他引:12
A human cDNA encoding the alpha subunit of casein kinase II and a partial cDNA encoding the rat homologue were isolated by using a Drosophila casein kinase II cDNA probe. The 2.2-kb human cDNA contains a 1.2-kb open reading frame, 150 nucleotides of 5' leader, and 850 nucleotides of 3' noncoding region. Except for the first 7 deduced amino acids that are missing in the rat cDNA, the 328 amino acids beginning with the amino terminus are identical between human and rat. The Drosophila enzyme sequence is 90% identical with the human casein kinase II sequence, and there is only a single amino acid difference between the published partial bovine sequence and the human sequence. In addition, the C-terminus of the human cDNA has an extra 53 amino acids not present in Drosophila. Northern analysis of rat and human RNA showed predominant bands of 5.5, 3.1, and 1.8 kb. In rat tissues, brain and spleen had the highest levels of casein kinase II alpha subunit specific RNA, while skeletal muscle showed the lowest. Southern analysis of human cultured cell and tissue genomic DNA using the full-length cDNA probe revealed two bands with restriction enzymes that have no recognition sites within the cDNA and three to six bands with enzymes having single internal sites. These results are consistent with the possibility that two genes encode the alpha subunits. 相似文献
4.
Cloning and characterization of a cDNA encoding the beta subunit of human casein kinase II 总被引:8,自引:0,他引:8
Previous studies [Summercorn et al. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8834-8838; Klarlung & Czech (1988) J. Biol. Chem. 263, 15872-15875] have indicated that Balb/c 3T3 cells and 3T3-L1 adipocytes incubated with insulin show increased casein kinase II activity within minutes, implicating this serine/threonine kinase as an early step in an insulin signaling pathway. We recently reported the isolation of a cDNA encoding an alpha subunit of human casein kinase II [Meisner et al. (1989) Biochemistry 28, 4072-4076] as an initial step toward examining the regulation of this enzyme. We now describe a HepG2 cell casein kinase II beta subunit cDNA of 2.57 kb containing 96 bases of 5' untranslated sequence, 645 bases of open reading frame, and 1832 bases of 3' untranslated sequence with two polyadenylation consensus signal sequences and two poly(A) stretches. The open reading frame of the human beta subunit cDNA was 77% and 87% identical with the Drosophila sequence at the nucleotide and amino acid levels, respectively, and 99% identical with the bovine amino acid sequence. RNA analysis of HepG2 cell RNA utilizing HepG2 beta subunit cDNA fragments as probes revealed one major band migrating at 1.2 kb and two minor bands migrating at 3.0 and 4.2 kb. Results from DNA analysis of HepG2 genomic DNA, consistent with results utilizing Drosophila genomic DNA, suggest the presence of a single gene for the beta subunit of casein kinase II. 相似文献
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The effect of endothelin-1 has been examined on isolated spontaneously beating right atria and electrically driven left atria from diabetic rats and age-matched controls. Diabetes was induced by a single i.v. injection of streptozotocin (65 mg/kg) 4–5 weeks before the experiments. Endothelin-1 (0.01–100 nM) caused concentration-dependent increases in atrial rate and force; the increases were not different between atria from diabetic and control rats. The ability of endothelin-1 to reduce chronotropic and inotropic responses to noradrenaline was also not different between the two groups. Endothelin-1 (10 nM) decreased the chronotropic response to sympathetic nerve stimulation (2 Hz, 10 s) in atria from control rats by 68 ± 5% (n = 8), but this decrease was slightly smaller (45 ± 6%, N = 8) in atria from diabetic rats.
The results provide no evidence to suggest that the diabetic state markedly alters cardiac responses to endothelin-1. 相似文献
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Lateral asymmetry refers to unequal fluorescent intensity between adjacent regions of sister chromatids. It has been observed in the centromeric regions of mitotic chromosomes of mouse or human origin when cells are grown in 5-bromo-2-deoxyuridine (BrdU) for a single round of DNA synthesis. The chromosome-orientation fluorescence in situ hybridization (CO-FISH) technique was used with pseudodiploid mouse cells to show that the regions of asymmetrical brightness coincide with major satellite repetitive DNA, and that the more heavily BrdU-substituted chromatid is the one that fluoresces less brightly. These observations support a 20 year old hypothesis on the origin of lateral asymmetry. Other observations suggest that differential loss of DNA from the heavily substituted chromatid also contributes to lateral asymmetry. 相似文献