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11.
Molecular Genetics and Genomics - 相似文献
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Diabetic nephropathy (DN), a major cause of end-stage chronic renal failure, is histologically characterized by glomerulosclerosis. To investigate the molecular mechanisms of DN, it is important to establish a stable model of glomerulosclerosis in mice, because genomic manipulation techniques (such as gene destruction or transgene insertion) are well established in rodent species. In this study, we found that repeated administrations of streptozotocin led to early onset of glomerular sclerotic lesions in C57BL/6 mice, accompanied with renal dysfunction. During the natural course of DN, glomerular endothelial cells decreased at 10 weeks after the start of streptozotocin-injections, whereas myofibroblastic mesangial cells became evident. Our results provide an animal tool to elucidate the molecular mechanisms of DN, for example to investigate vascular pathology in diabetic glomerular diseases. 相似文献
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Kuo Huang Ling Bai Jiun Chen Yun Wen Peng Shih Chong Tsai Fu Chuo Peng Chung Kuang Yang 《Mycotoxin Research》1987,3(2):58-64
The chemical reaction of cleavaging territrem B to give 3,4,5-trimethoxy benzoic acid by alkaline hydrogen peroxide was investigated. The method was applied for confirmation of the chemical structure of the aromatic moiety of territrem A, A’, B, and B’. The physicochemical properties of the aromatic cleavage product of territrem Aindicated the structure as 3,4-methylendioxy, 5-methoxy benzoic acid (or 4-methoxy, 6-carboxy, 1, 3-benzodioxole). The experiment also gave the evidences that territrem A and A’, on the other hand territrem B and B’ have the identical aromatic moieties on their structures. 相似文献
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In a previous publication (Narhi, L. O., and Fulco, A. J. (1986) J. Biol. Chem. 261, 7160-7169) we described the characterization of a 119,000-dalton P-450 cytochrome that is strongly induced by barbiturates in Bacillus megaterium. In the presence of NADPH and O2, this single polypeptide can catalyze the hydroxylation of long-chain fatty acids without the aid of any other protein. The gene encoding this unique monooxygenase (cytochrome P-450BM-3) has now been cloned by an immunochemical screening technique. The Escherichia coli clone harboring the recombinant plasmid produces a 119,000-dalton protein that appears to be electrophoretically and immunochemically identical to the B. megaterium enzyme and contains the same N-terminal amino acid sequence. The recombinant DNA product also exhibits the characteristic cytochrome P-450 spectrum and is fully functional as a fatty acid monooxygenase. In E. coli, the synthesis of P-450BM-3 is directed by its own promoter included in the DNA insert and proceeds constitutively at a very high rate but is not stimulated by pentobarbital. However, when the cloned P-450BM-3 gene, either intact or in a truncated form, is introduced back into B. megaterium via an E. coli/Bacillus subtilis shuttle vector, its expression is constitutively repressed but is induced by pentobarbital. This finding demonstrates that the regulatory region of the P-450BM-3 gene that responds to barbiturates is included in the cloned DNA. The evidence also indicates that pentobarbital cannot directly act on the gene to cause induction but presumably interacts with another component such as a repressor molecule that is present in B. megaterium but is absent in the E. coli clone. 相似文献
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H D S?ling E Machado-DeDomenech J Kleineke W Fest 《The Journal of biological chemistry》1987,262(35):16786-16792
The early effects (0-120 s) of the beta-adrenergic secretagogue isoproterenol (2.10(-5) M) and the muscarinic secretagogue carbamoylcholine (2.10(-6) M) on various parameters of lipid and phospholipid metabolism were studied in isolated guinea pig parotid acinar cells. Both agonists enhanced within 10-20 s the incorporation of radioactive palmitate into the diacylglycerol, the triglyceride, and the phosphatidylinositol fractions but significantly diminished radioactive palmitate recovered in the acyl-CoA fraction. Carbamoylcholine decreased and isoproterenol increased the recovery of radioactive palmitate in the free fatty acid fraction. All changes had returned almost to control levels after 120 s. In cells prelabeled with [3H]arachidonate, carbamoylcholine exerted similar effects, whereas isoproterenol was almost ineffective. Both agonists stimulated the incorporation of radioactive glycerol into diacylglycerols 2-3-fold, while only carbamoylcholine stimulated the incorporation of [32P]phosphate into phosphatidylinositol and phosphatidate. Both agonists induced an increase in total diacylglycerols, carbamoylcholine being about twice as effective as isoproterenol. A lower concentration of carbamoylcholine (6.5.10(-7) M) had the same quantitative effect as 2.10(-5) M isoproterenol on the increase of total diacylglycerols. Even under these conditions carbamoylcholine, but not isoproterenol led to a significant translocation of protein kinase C from the soluble to the particulate fraction. Isoproterenol remained ineffective in this respect also when intracellular free calcium was increased with a calcium ionophore. This is explained by the finding that isoproterenol stimulates preferentially the formation of 2,3-sn-diacylglycerol, and carbamoylcholine preferentially stimulates the formation of 1,2-sn-diacylglycerol. The results indicate that in the guinea pig parotid acinar cell the two agonists do not only lead to activation of a triglyceride lipase (isoproterenol) or phosphoinositide-specific phospholipase(s) (carbamoylcholine), but also to a rapid change of flux through a number of other enzyme-catalyzed reactions involved in diacylglycerol turnover. 相似文献
20.
C Domenech E Machado-De Domenech H D S?ling 《The Journal of biological chemistry》1987,262(12):5671-5676
Stimulation of secretion in guinea pig exocrine cells is associated with an enhanced synthesis in these cells of 1-O-alkyl-2-sn-acetyl-glycero-3-phosphocholines (PAF) from 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (S?ling, H-D., and Fest, W. (1986) J. Biol. Chem. 261, 13916-13922). This results from a stimulation of the activity of lyso-1-alkylglycerophosphocholine acetyltransferase (EC 2.3.1.67). Here we have analyzed the effects of various agonists on the activity of this enzyme in guinea pig parotid gland microsomes. Carbamoylcholine leads within less than 30 s to a 2- to 4-fold activation of lyso-PAF-acetyltransferase, which persists after solubilization of the microsomal enzyme with octyl glucoside. The calcium ionophore A23187 has a similar though smaller effect. Neither isoproterenol (2 X 10(-5) M), which stimulates exocytosis more than carbachol, nor phorbol ester significantly affected lyso-PAF-acetyltransferase activity. Incubation of microsomes from unstimulated parotid gland acini with cAMP-dependent and calcium/calmodulin-dependent protein kinase resulted in a 4-fold and 2.9-fold activation of lyso-PAF-acetyltransferase activity, respectively. Protein kinase C had no significant effect. Activation with calcium/calmodulin-dependent protein kinase was inhibited by 40 microM trifluoperazine. When microsomes from carbachol-stimulated glands were used, in vitro activation of the enzyme by calcium/calmodulin-dependent protein kinase was almost abolished. Protein phosphatase 2A in vitro strongly reduced lyso-PAF-acetyltransferase activity in microsomes from both stimulated and unstimulated glands, whereas alkaline phosphatase and protein phosphatase 1 had only small effects. Following treatment with protein phosphatase 2A, enzyme activity in microsomes from stimulated glands could be enhanced more than 8-fold by subsequent incubation with calcium/calmodulin-dependent protein kinase. Although unsuccessful attempts have made it impossible so far to demonstrate directly the incorporation of phosphate into lyso-PAF-acetyltransferase, the results reported here strongly suggest that the enzyme in exocrine cells is regulated by phosphorylation-dephosphorylation and that a calcium/calmodulin-dependent protein kinase is responsible for the activation of the enzyme and type-2 protein phosphatases for its inactivation. 相似文献