摘要:

Elevated glomerular filtration rate (GFR) is a frequent finding in patients with early insulin‐dependent diabetes mellitus (IDDM). The mechanisms responsible for this glomerular hyperfiltration in IDDM are unclear. Rats made diabetic with alloxan or streptozotocin, and treated daily with supplemental insulin, have moderate hyperglycemia and elevated GFR, and thus have been used to study mechanisms of glomerular hyperfiltration in diabetes. Renal micropuncture techniques have shown that single‐nephron GFR (SNGFR) is elevated in moderately hyperglycemic diabetic rats. In some cases, this is because of elevated glomerular capillary pressure (Pgc), but in other cases, Pgc is normal despite elevated SNGFR. Several potential mediators of increased SNGFR have been examined, including hyperglycemia, increased glomerular prostaglandin production, and decreased sensitivity of the tubuloglomerular feedback mechanism. Renal failure is a common complication of human IDDM. Diabetic rats with long‐term moderate hyperglycemia have been used to study the mechanisms by which glomerular injury develops in diabetes mellitus. It has been postulated that glomerular hyperfiltration or some determinant of elevated GFR in early diabetes may ultimately cause glomerular damage, leading to a progressive loss of renal function (diabetic nephropathy). Diabetic rats with long‐term moderate hyperglycemia, however, do not develop characteristic glomerular lesions of human diabetic nephropathy and, in fact, develop only minimal glomerular injury even after 1 year of diabetes. Thus, although the diabetic rat with moderate hyperglycemia may be useful to study the mechanisms of glomerular hyperfiltration in early diabetes, it may not be an appropriate model of renal failure in IDDM.— O'Donnell, M. P.; Kasiske, B. L.; Keane, W. F. Glomerular hemodynamic and structural alterations in experimental diabetes mellitus.FASEB J.2: 2339‐2347; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.3282959

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Protein kinase C is activated by the simultaneous presence of phospholipid, a diglyceride, and Ca2+. Under physiological conditions the activity of the enzyme is regulated by the availability of diglycerides, which are the products of phosphoinositide hydrolysis. The phospholipid‐kinase interactions appear not to be of a highly specific nature. Phosphatidylserine (PS) is presumed to be the endogenous lipid that interacts with the kinase, but other acidic lipids can substitute. On the other hand, the kinase‐diglyceride interactions are highly specific in nature, as would be expected of a physiological regulator. These interactions are stereospecific and stoichiometric with respect to diglyceride. The specificity is directed toward the glycerol backbone and hydrophilic oxygen moieties of the diglyceride. The removal of one or more of the oxygen atoms or the addition of a single methyl group to the glycerol backbone virtually abolishes the activity of a putative diglyceride activator. The extreme specificity of the kinase toward the diglycerides, however, must be contrasted with the abilities of structurally diverse tumor promotors and irritants to activate the kinase. Specific small‐molecule antagonists of protein kinase C have yet to be developed. The small‐molecule antagonists that have been developed so far have been relatively nonspecific cationic lipids that appear to function by interfering with the interaction between the acidic phospholipids and Ca2+.— Rando, R. R. Regulation of protein kinase C activity by lipids.FASEB J.2: 2348‐2355; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.3282960

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

G proteins that serve to transduce external signals in membranes share with protein synthesis factors and tubulin structural and functional features that are common to proteins that participate in reversible GTP‐mediated macromolecular interactions. These proteins can bind GTP and GDP with high affinity, adopting different structures depending on whether they are complexed with the nucleotide diphosphate or triphosphate. The GTP · protein complex has high affinity for an acceptor macromolecule (or complex of macromolecules) and interacts with it, affecting its activity. These GTP‐binding proteins also possess an intrinsic GTPase activity that is generally stimulated by its interaction with the acceptor. The GTPase activity converts the bound GTP to GDP, switching the configuration of the complexed protein to one of low affinity for the acceptor and causing its dissociation. The protein · GDP complex must exchange its GDP for GTP to allow the protein to acquire the high‐affinity structure that can cycle back to the acceptor macromolecule. This exchange of guanine nucleotides requires in several instances exchange factors that can regulate the whole process. A detailed comparison of the features of the different systems is made with respect to structural similarities, regulation by protein phosphorylation, ADP ribosylation by bacterial toxins, and requirements for exchange factors. It is also proposed that there is a similar mechanism that involves ATP/ADP‐binding proteins.—Allende,j. E. GTP‐mediated macromolecular interactions: the common features of different systems.FASEB J.2: 2356‐2367; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.2452111

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Quantitative contributions of the direct and indirect pathways to liver glycogen formation from a glucose load have been estimated from1) the distribution of label in glycogen formed from specifically carbon‐labeled loads of glucose,2) the specific activity of the glycogen compared with that of the circulating glucose,3)the3H:14C ratios in glycogen formed from loads specifically labeled with3H and14C,4) the incorporation of3H from3H2O into the glycogen, and5) the balance of glucogenic substrates across the splanchnic bed. A number of assumptions are made in the use of each of these methods. Estimates have been made for animals and humans fasted overnight or longer. Results obtained with the different methods are compared. Under these conditions, the contribution of the pathways appears to be determined by the size of the load, with larger contributions of the indirect pathway occurring with smaller loads.— Landau, B. R.; Wahren, J. Quantification of the pathways followed in hepatic glycogen formation from glucose.FASEB J.2: 2368‐2375; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.3282961

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Spontaneously occurring autoantibody to threonyl‐tRNA synthetase found in the serum of patients with polymyositis and experimentally induced antibody against highly purified rabbit reticulocyte threonyl‐tRNA synthetase were used to analyze the epitopes of threonyl‐tRNA synthetase. The PL‐7 autoantibody reacted with the native but not the denatured form of threonyl‐tRNA synthetase, whereas the experimentally induced antibody recognized both the native and denatured forms of the enzyme. In addition, the PL‐7 autoantibody specifically inhibited threonyl‐tRNA synthetase activity whereas the experimentally induced antibody had no effect on aminoacylation. Thus, the epitopes recognized by the PL‐7 autoantibody are formed by the tertiary structure of the enzyme and are associated with the catalytic site of the synthetase whereas the experimentally induced antibody recognizes epitopes formed by primary sequences not related to the catalytic function of the synthetase.— Dang, C. V.; Tan, E. M.; Traugh, J. A. Myositis autoantibody reactivity and catalytic function of threonyl‐tRNA synthetase.FASEB J.2: 2376‐2379; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.2452112

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

The Thomsen‐Friedenreich (T) antigen and its disaccharide component Galβ1,3GalNAc, which is recognized by the plant lectin peanut agglutinin (PNA), have been proposed as useful tumor markers because of their apparently specific occurrence in certain types of carcinomas. We have investigated the mechanism for the appearance of the disaccharide at the cell surface of ascites 13762 rat mammary adenocarcinoma cells using pulse‐chase glucosamine labeling, proteolysis, and PNA precipitation of the cell‐surface sialomucin ASGP‐1. Glucosamine‐labeled disaccharide appears at the cell surface in less than 10 min. Although the appearance of larger oligosaccharides continues to increase, the appearance of labeled disaccharide levels off within an hour. Analysis of intracellular vs. cell surface‐labeled oligosaccharides showed that all disaccharide synthesized more than an hour before reaching the cell surface is converted to larger oligosaccharides. Thus, the presence of the disaccharide at the cell surface results from its synthesis late in the transit pathway of the sialomucin tb the cell surface. We propose that the presence of T antigen at the surface of carcinoma cells results from an aberration of the pathway for O‐linked glycosyiation in these cells, probably caused by inappropriate localization of the enzymes involved in synthesis of the disaccharide.—Hull, S. R.; Carraway, K. L. Mechanism of expression of Thomsen‐Friedenreich (T) antigen at the cell surface of a mammary adenocarcinoma.FASEB J.2: 2380‐2384; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.3360239

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

A panel of monoclonal and polyclonal antibodies raised against human platelet GpIb or the GpIIb/IIIa complex were used to detect immunologically related molecules on two cell lines derived from human solid tumors. Human cervical carcinoma (MS751) and human colon carcinoma (clone A) expressed molecules immunologically related to platelet GpIb and GpIIb/IIIa complex. These molecules were localized to their plasma membranes by immunofluorescence and immunocytochemistry. The immunologically related GpIb was evenly distributed on the tumor cell membrane with occasional areas of aggregates, whereas the immunologically related GpIIb/IIIa had a pronounced punctate distribution of aggregates in prefixed cells. When MS751 or clone A cells were pretreated with antibodies against platelet GpIb and/or the GpIIb/IIIa complex, their ability to induce platelet aggregation was significantly inhibited. In addition, when tumor cells were pretreated with antibodies against the platelet IIb/IIIa complex, adherence to fibronectin‐coated plates was also significantly inhibited. These results suggest a role for these immunologically related tumor cell glycoproteins in tumor cell‐host cell (i.e., platelet, endothelial cells) interactions, tumor cell interactions with components of the subendothelial matrix, and subsequent tumor metastasis.—Grossi, I. M.; Hatfield, J. S.; Fitzgerald, L. A.; Newcombe, M.; Taylor, J. D.; Honn, K. V. Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and Ilb/IIIa in tumor cell‐platelet and tumor cell‐matrix interactions.FASEB J.2: 2385‐2395; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.2452113

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

The synthetase that attaches biotin to the aposubunit of transcarboxylase (biotin‐[methylmalonyl‐CoA‐car‐boxyltransferase]ligase) (EC 6.3.4.9) was purified to homogeneity by ion‐exchange chromatography on cellulose DE‐52 and CM‐cellulose. The synthetase is a monomer of molecular weight 30,000. The pH and temperature optima for the synthetase are 6.0 and 37°C, respectively. The apparentKmfor the substrates ATP, biotin, and apo 1.3S subunit of apotranscar‐boxylase are 38, 2.0, and 0.9 μM, respectively. Ni2+, Co2∗, Zn2+, or Mn2+could replace Mg2+in the reaction. The affinity of synthetase toward metals is as follows: Zn2+>Ni2+>Mn2+>Co2+>Mg2+, and the activity with Zn2+was much greater than that with the other divalent metals. EDTA completely inactivates the enzyme. The metals are necessary not only for the catalytic activity but also for the storage stability of the enzyme. The synthetase shows absolute specificity toward ATP.— Shenoy, B. C.; Wood, H. G. Purification and properties of the synthetase catalyzing the biotination of the aposubunit of transcarboxylase fromPropionibacterium shermanii FASEB J.2: 2396‐2401; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.3360240

出版商:Wiley    

年代:1988

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.3360241

出版商:Wiley    

年代:1988

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.2.8.3360242

出版商:Wiley    

年代:1988

数据来源: WILEY