Biochemical medicine and metabolic biology最新文献

{"title":"Glutathione Metabolism in Crohn′s Disease","authors":"Iantomasi T.,&nbsp;Marraccini P.,&nbsp;Favilli F.,&nbsp;Vincenzini M.T.,&nbsp;Ferretti P.,&nbsp;Tonelli F.","doi":"10.1006/bmmb.1994.1062","DOIUrl":"10.1006/bmmb.1994.1062","url":null,"abstract":"<div><p>A statistically significant decrease of glutathione (GSH) and an increase of GSH disulfide (GSSG) both in healthy and ill ileum of patients with Crohn′s disease in comparison with the controls (without this pathology) is demonstrated. However, the lowering of these levels was more remarkable in ill ileum in which high levels of GSSG were detected, too. These alterations may be in part explained by the changes obtained in GSH-related enzyme levels. Finally, considering the results that others and we obtained by studies on GSH oral absorption in rat intestine, an oral therapy of GSH in Crohn′s disease is suggested.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 2","pages":"Pages 87-91"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18714765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatic and Secretory Activities in Pancreatic-Islets of Non-Insulin-Dependent Diabetic Rats after Short-Term Infusion of Succinic Acid Monomethyl Ester","authors":"Giroix M.H.,&nbsp;Sener A.,&nbsp;Portha B.,&nbsp;Malaisse W.J.","doi":"10.1006/bmmb.1994.1066","DOIUrl":"10.1006/bmmb.1994.1066","url":null,"abstract":"<div><p>The monomethyl ester of succinic acid (SME) was recently proposed as a novel tool for stimulation of proinsulin biosynthesis and insulin release in animal models of non-insulin-dependent diabetes mellitus. In the present study, either saline or SME (14 mmol/day) was infused for 3 days to control rats, animals injected with streptozotocin during the neonatal period, and Goto-Kakizaki rats with inherited diabetes. The infusion of SME failed to correct the anomalies found in the islets of diabetic rats, namely, a decreased activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, a low insulin content, and an impaired secretory response to various nutrient secretagogues including D-glucose, 2-ketoisocaproate, and the combination of L-leucine and L-glutamine. These findings raise the question of whether a more prolonged administration of SME is required to raise the insulin store and improve the secretory potential of the endocrine pancreas in animals with type 2 diabetes.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 2","pages":"Pages 115-121"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18714759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylated Purine Bases in Hepatic and Colonic RNA of Rats Treated with 1,2-Dimethylhydrazine","authors":"Kang J.O.","doi":"10.1006/bmmb.1994.1057","DOIUrl":"10.1006/bmmb.1994.1057","url":null,"abstract":"<div><p>Administration of 1,2-dimethylhydrazine (DMH) to rats produces colon cancer. The mechanism by which this agent induces colon cancer is unclear. This investigation was conducted to assess the effect of DMH on the hepatic RNA and the colonic RNA of rats. DMH (300 mg/kg body wt) was administered to rats by ip injections. After 24 h, the hepatic RNA and the colonic RNA were isolated and their component purine bases were analyzed by HPLC. DMH treatment resulted in the formation of 1-methyladenine, 1-methylguanine, N²-methylguanine, O⁶-methylguanine, and 7-methylguanine in RNA. These methylated products may play a role in cellular injury produced by DMH.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 52-57"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18538743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homozygous Presence of the Crossover (Fusion Gene) Mutation Identified in a Type II Gaucher Disease Fetus: Is This Analogous to the Gaucher Knock-out Mouse Model?","authors":"Strasberg P.M.,&nbsp;Skomorowski M.A.,&nbsp;Warren I.B.,&nbsp;Hilson W.L.,&nbsp;Callahan J.W.,&nbsp;Clarke J.T.R.","doi":"10.1006/bmmb.1994.1052","DOIUrl":"10.1006/bmmb.1994.1052","url":null,"abstract":"<div><p>Gaucher disease (GD) is an inherited deficiency of β-glucocerebrosidase (EC 3.1.2.45, gene symbol <em>GBA</em>). In type I GD, the CNS is not involved (nonneuronopathic), whereas in type II GD (acute neuronopathic) CNS involvement is early and rapidly progressive, while in type III GD (subacute neuronopathic) CNS involvement occurs later and is slowly progressive. The T6433C (L444P) substitution is prevalent in type GD II. It may occur alone as a single base-pair mutation but often is found as part of a complex allele containing additional <em>GBA</em> nucleotide substitutions, G6468C (A456P) and G6482C (V460V), without (recNciI) or with (recTL) G5957C (D409H). This complex allele is presumed to have formed by recombination (crossover, fusion) of the structural gene with the pseudogene, which contains the mutated sequences. Two complex alleles have never been demonstrated to coexist in any individual. We devised a selective PCR method for the specific amplification of the normal and/or fusion gene. Using this procedure we demonstrated the fusion gene in homozygous form for the first time, in a Macedonian/Ashkenazi Jewish GD type II fetus. Both parents were carriers of the recombination. This was confirmed by direct sequence analysis. A previous conceptus in this family was stillborn at 36 weeks, with features of severe type II GD. Neonates showing a severe clinical phenotype, analogous to the early neonatal lethal disease occurring in mice homozygous for a null allele produced by targeted disruption of <em>GBA</em>, have been described elsewhere, but the specific mutations in these cases have not yet been characterized. We suggest that this genotype is lethal, as in the mice, and may account for some or all of the mutations in the neonates.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 16-21"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18855480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Protein Kinase C on the Plasma Membrane Calcium Pump in Purified Beta Cells","authors":"Hoenig M.,&nbsp;Knutson K.L.","doi":"10.1006/bmmb.1994.1060","DOIUrl":"10.1006/bmmb.1994.1060","url":null,"abstract":"<div><p>The effect of protein kinase C activation on (Ca²⁺-Mg²⁺)-ATPase and ⁴⁵Ca²⁺ uptake in purified plasma membranes and membrane vesicles from beta cells was examined. PKC activation was achieved by incubating cells for 10 or 30 min in 100 nM or 1 μM of the phorbol ester 12-<em>O</em>-tetradecanoylphorbol 13-acetate (TPA) and evident by translocation of the α-isoform from the cytosolic to the membrane fraction. (Ca²⁺-Mg²⁺)-ATPase had a <em>K_m</em> for Ca²⁺ of 0.56 ± 0.17 μM and the <em>V</em>_max was 120 ± 12 nmol/min*mg protein in membranes from cells treated with TPA, while it was 0.66 ± 0.14 μM and 135 ± 19 nmol/min*mg protein, respectively, in its absence. In inside-out vesicles ⁴⁵Ca²⁺ uptake had a <em>K_m</em> for Ca²⁺ of 79 ± 19 nM and a <em>V</em>_max of 1.68 ± 0.43 nmol/min*mg protein in the presence of TPA. In the absence of TPA, the <em>K_m</em> was 71 ± 17 mM, and the <em>V</em>_max was 1.59 ± 0.39 nmol/min*mg mg protein, respectively. It is concluded that in beta cells PKC activation does not regulate (Ca²⁺-Mg²⁺)-ATPase activity or Ca²⁺ transport directly.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 75-79"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18857452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial Adaptation to Long-Term Action of Substances Associated with Decreased Intensity of Cardiac Function","authors":"Veksler V.I.,&nbsp;Levitskaya E.L.,&nbsp;Khatkevich A.N.,&nbsp;Orekhova I.V.,&nbsp;Khuchua Z.A.,&nbsp;Kapelko V.I.","doi":"10.1006/bmmb.1994.1051","DOIUrl":"10.1006/bmmb.1994.1051","url":null,"abstract":"<div><p>The effect of prolonged treatment of rats with 6-<em>n</em>-propyl-2-thiouracil (PTU), verapamil, or propranolol on cardiac pump function and the properties of myofibrils and mitochondria was studied. After 6-8 weeks of treatment, the heart rate and maximal cardiac output of the isolated heart of rats treated with verapamil or propranolol were higher than those in the control group. The PTU treatment was followed by lower heart rate and maximal work. Calcium sensitivity (<em>p</em>Ca₅₀ value) of skinned ventricular fibers was higher in all experimental groups compared to the control by 0.07-0.15 units. Myofibrillar Mg²⁺, Ca²⁺-ATPase activity measured in isolated Triton-skinned cardiomyocytes was considerably lower after PTU treatment than that in respective controls (0.128 ± 0.013 vs 0.178 ± 0.010 μmol <em>P</em>_i/min/mg protein). In contrast, long-term treatment with verapamil or propranolol was accompanied by increased activity to 0.223 ± 0.018 and 0.254 ± 0.015 μmol <em>P</em>_i/min/mg protein, respectively. Neither the basal mitochondrial respiration rate of saponin-skinned cardiac fibers nor its enhancement after addition of low ADP concentration or creatine was significantly altered in any experimental group. Also no difference between control and experimental groups was observed in the total activity of creatine kinase or relative percentage of its isoenzymes extracted from cardiac tissue. Thus the changes in cardiac pump function after prolonged treatment with agents decreasing cardiac function may be attributed to concomitant alterations of myofibrils while mitochondria remain relatively intact.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 8-15"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18857453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Action of Succinic Acid Monomethyl Ester Against the Impairment of Glucose-Stimulated Insulin Release Caused by Glucopenia or Starvation: Metabolic Determinants","authors":"Eizirik D.L.,&nbsp;Welsh N.,&nbsp;Sener A.,&nbsp;Malaisse W.J.","doi":"10.1006/bmmb.1994.1055","DOIUrl":"10.1006/bmmb.1994.1055","url":null,"abstract":"<div><p>The monomethyl ester of succinic acid (SME) was recently found to protect pancreatic islet B-cells against the impairment of glucose-stimulated insulin release caused by either glucopenia or starvation. The possible metabolic determinants of such a protective action are now scrutinized. After 180 min preincubation at 2.8 mM D-glucose in the presence of SME (10 mM), the oxidation of D-[U-¹⁴C]glucose, relative to either the utilization of D-[5-³H]glucose or the generation of ¹⁴C-labeled acidic metabolites, was higher than that after preincubation in the absence of SME, and became close to that otherwise found after preincubation at 16.7 mM D-glucose. Likewise, after 3 days of culture at a low concentration of D-glucose (2.8 nM), the presence of SME in the culture medium tended to increase the subsequent oxidation of D-[6-¹⁴C]glucose and utilization of D-[5-³H]glucose. These two variables increased as a function of the concentration of D-glucose in the culture medium, this coinciding with a modest increase in hexokinase activity and a more pronounced increase in glucokinase activity. The presence of SME in the culture medium failed, however, to exert any obvious effect upon the respiration of the islets, suggesting that the protective action of the ester against glucopenia may also involve variables distinct from the metabolism of either endogenous or exogenous nutrients. Likewise, the fact that SME infusion to starved rats prevents the impairment of glucose-induced insulin release otherwise attributable to starvation may involve enzymatic determinants, such as a less severe decrease in glucokinase activity, metabolic variables, such as a greater relative increase in D-[U-¹⁴C]glucose oxidation relative to D-[5-³H]glucose utilization in response to a rise in extracellular D-glucose concentration, and other factors yet to be identified that-participate in the secretory sequence at a site distal to those metabolic events triggered by D-glucose in the islet cells.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 34-45"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18855483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonkallikrein Arginine Endopeptidase in the Human Submaxillary Gland: Purification and Characterization of the Enzyme","authors":"Watanabe Y.,&nbsp;Suzuki M.,&nbsp;Fujimoto Y.","doi":"10.1006/bmmb.1994.1056","DOIUrl":"10.1006/bmmb.1994.1056","url":null,"abstract":"<div><p>The two major species of arginine endopeptidase present in the soluble fraction of human submaxillary gland are glandular kallikrein and another enzyme tentatively named nonkallikrein arginine endopeptidase. In this study, we purified the latter enzyme to homogeneity and examined its catalytic properties. The newly found enzyme was clearly distinguishable from human tissue kallikrein in its molecular nature, action toward various synthetic substrates, and kinin-generated activity. The specificity of the action of the enzyme was further investigated using various basic amino acid-containing peptides as model substrates. HPLC analysis of peptide fragments produced, followed by their amino acid analysis, revealed that the enzyme preferentially hydrolyzed the Arg-Arg or Arg-Lys bonds in dynorphins A 1-10, 1-9, and 1-8, β-neoendorphin, adenorphin, and neurotensin.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 46-51"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18855484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulinotropic Action of Formycin A","authors":"Malaisse W.J.,&nbsp;Sener A.,&nbsp;Gruber H.E.,&nbsp;Erion M.D.","doi":"10.1006/bmmb.1994.1053","DOIUrl":"10.1006/bmmb.1994.1053","url":null,"abstract":"<div><p>The adenosine analogue formycin A is phosphorylated to its triphosphate ester in a sequence of reactions catalyzed by adenosine kinase and adenylate kinase. Formycin A triphosphate is an ATP analogue that is currently used to probe for ATP binding sites. Considering the key role ascribed to ATP in the coupling of metabolic to cationic events in the process of glucose-stimulated insulin release, we investigated whether formycin A displays insulinotropic action in rat pancreatic islets. Formycin A (10 μM to 1.0 mM) caused a concentration-related increase of insulin release evoked by 8.3 mM D-glucose and prevented the fall in insulin output otherwise observed over two successive incubations of 90 min each. Formycin A (1.0 mM) also augmented insulin secretion at low (5.6 mM) and high (16.7 mM) concentrations of D-glucose. At the low hexose concentration, the secretory response to formycin A was comparable to that evoked by either glibenclamide or glipizide. At higher concentrations of D-glucose, however, formycin A was more potent than the hypoglycemic sulfonylureas in enhancing insulin output. These findings support the role of ATP in glucose-stimulated insulin release and, therefore, suggest that ATP mimetics represent a new class of insulinotropic agents that have potential utility in the treatment of non-insulin-dependent diabetes mellitus.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 22-27"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18855481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunochemical Characterization of Feline and Human N-Acetylgalactosamine 4-Sulfatase","authors":"Brooks D.A.,&nbsp;Gibson G.J.,&nbsp;Hopwood J.J.","doi":"10.1006/bmmb.1994.1058","DOIUrl":"10.1006/bmmb.1994.1058","url":null,"abstract":"<div><p>Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is a disorder which results from a deficiency in the lysosomal associated enzyme <em>N</em>-acetylgalactosamine 4-sulfatase (4-sulfatase). A feline model of human MPS VI has previously been described and provides a system for the evaluation of enzyme replacement therapy protocols. As a preliminary study to human 4-sulfatase enzyme replacement therapy in feline we have compared the immunochemical properties of human and feline 4-sulfatase. By SDS-PAGE the molecular mass of purified feline and human 4-sulfatase were similar under both reducing and nonreducing conditions. There was, however, a detectable conformation difference between human and feline 4-sulfatase indicating some structural variation. Feline 4-sulfatase reacted weakly with a panel of monoclonal antibodies in an immunobinding assay (interacting with 4-sulfatase in free solution), but the same monoclonal antibodies reacted strongly with feline 4-sulfatase in an immunoquantification assay where the feline 4-sulfatase was bound to a polyclonal antibody (which presumably induces a conformation change in the feline 4-sulfatase to closer approximate the structure of human 4-sulfatase). A monoclonal antibody which selectively reacts with human 4-sulfatase has been used to develop an assay suitable for evaluating human 4-sulfatase enzyme replacement in cat tissues.</p></div>","PeriodicalId":8752,"journal":{"name":"Biochemical medicine and metabolic biology","volume":"53 1","pages":"Pages 58-66"},"PeriodicalIF":0.0,"publicationDate":"1994-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmmb.1994.1058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18855485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}