Febs Letters

doi: 10.1016/0014-5793(93)80951-Ppmid: N/A

Fesus, Laszlo

doi: 10.1016/0014-5793(93)80952-Qpmid: 8344412

Several molecular elements of programmed cell death and apoptosis have recently been revealed. The function of gene products which deliver the lethal ‘hit’ is still not known. Well‐characterized and newly discovered cell surface structures (e.g. antigen receptors, FAS/APO‐1), as well as transcriptional factors (steroid receptor, c‐myc, P53, retinoblastoma protein and others), have been implicated in the initiation of the death pathway. Negative regulators of the process (ced‐9 gene product in programmed death of cells in Chaenorhabditis elegans and bcl‐2 protein in apoptosis) have been described. Biochemical mechanisms responsible for the silent nature of natural deaths of cells include their rapid engulfment (mainly through integrin receptors), transglutaminase‐catalyzed cross‐linking of cellular proteins, and fragmentation of DNA. Several lines of evidence suggest that distinct molecular mechanisms may operate in various forms of natural cell death.

Vener, Alexander V.; Aksenova, Marina V.; Burbaeva, Gulnur Sh.

doi: 10.1016/0014-5793(93)80953-Rpmid: 7688325

Tyrosine phosphorylation of proteins from postmortem hippocampi of five Alzheimer's disease and five control cases have been compared. It was found that addition of Zn2+ or Mg2+ to membrane fractions of control hippocampi caused the phosphorylation of 32‐, 40‐, 55‐, 60‐, 80‐ and 100‐kDa proteins or 43‐, 55‐, 60‐ and 90‐KdA proteinsrespectively. The phosphorylation of all these proteins is shown to be drastically reduced in Alzheimer's disease hippocampi. Vanadate an inhibitor of protein tyrosine phosphataseshad no influence on the level of protein phosphorylation. Western blot analysis did not reveal any differences in the anti‐phosphotyrosine immunoreactive membrane proteins from Alzheimer's disease and control hippocampi. Tyrosine kinase activity of immunoprecipitated p60c‐src from Alzheimer's disease and control hippocampi were the same. In conclusion, the Zn2+‐ and Mg2+ ‐stimulated tyrosine kinase activities distinct from activity of p60c‐src are decreased in Alzheimer's disease hippocampus.

Kleemann, Rainer; Rothe, Helga; Kolb-Bachofen, Victoria; Xie, Qiao-wen; Nathan, Carl; Martin, Stephan; Kolb, Hubert

doi: 10.1016/0014-5793(93)80954-Spmid: 7688327

The inducible NO synthase (iNOS) was found to be expressed in pancreatic lesions of adult diabetes‐prone BB rats. Pancreatic iNOS mRNA was detected by reverse transcriptase PCR in pancreatic RNA of adult diabetes‐prone BB rats but not in normal Wistar rats, young diabetes‐prone BB rats without insulitis or in diabetes‐resistant BB rats. Immunohistochemistry of pancreatic sections using an iNOS‐specific antiserum labeled the pancreas of adult diabetes‐prone BB rats but not Wistar rats. Parallel staining for EDI‐positive macrophages showed restriction of iNOS expression to areas of islet infiltration by macrophages. In conclusion, the data provide direct evidence for enhanced expression of inducible NO synthase in tissue lesions during the development of autoimmune diabetes.

Rueda, Ricardo; Tabsh, Khalil; Ladisch, Stephan

doi: 10.1016/0014-5793(93)80955-Tpmid: 8344418

Gangliosides are possibly very potent immunosuppressive molecules. Here we show that human amniotic fluid contains high concentrations of a number of previously unnoted, structurally complex and highly polar gangliosides. These unusual molecules are present early in pregnancy (first trimester), increase in concentration with gestational age, and reach maximum levels (0.8 μM) at term. Since similar gangliosides have been detected in human placenta, trophoblast, and amnion, we suggest that these molecules are shed into the amniotic fluid bathing these tissues.

Suzuki, Masashi; Itoh, Takehiro; Osada, Hiroyuki; Rubin, Jeffrey S.; Aaronson, Stuart A.; Suzuki, Tohru; Koga, Nobumitsu; Saito, Takao; Mitsui, Youji

doi: 10.1016/0014-5793(93)80956-Upmid: 8344423

A heparin‐binding mitogen rat for rat hepatocytes was partially purified from bovine spleen by a combination of heparin‐affinity, cation‐exchange and gel‐filtration chromatography. Besides stimulating rat hepatocytes, this factor, which was designated spleen‐derived growth factor‐3 (SDGF‐3), exhibited mitogenic activity for mouse epidermal keratinocytes but not mouse fibroblasts. Its apparent epithelial specificity and heparin‐binding properties corresponded to those of keratinocyte growth factor (KGF). These findings, together with the fact that the mitogenic activity of SDGF‐3 was abolished by a neutralizing monoclonal antibody specific for KGF, identify this bovine spleen‐derived hepatocyte mitogen as KGF.

Koda, Toshiaki; Kakinuma, Mitsuaki

doi: 10.1016/0014-5793(93)80957-Vpmid: 7688322

A cDNA encoding a small GTP‐binding protein, S10, was cloned from Jurkat cells. The deduced amino acid sequence of S10 had the structural features characteristic to this family of proteins with highest homology to rab subfamily. Northern blot analysis revealed that this gene is expressed only in lymphoid cell lines and a histiocytic leukemia, U937. Hence, it should have a specialized function in cells derived from the hematopoietic stem cell.

Komada, Masayuki; Hatsuzawa, Kiyotaka; Shibamoto, Sayumi; Ito, Fumiaki; Nakayama, Kazuhisa; Kitamura, Naomi

doi: 10.1016/0014-5793(93)80958-Wpmid: 8344430

The hepatocyte growth factor/scatter factor (HGF/SF) receptor consists of an α‐ and a β‐subunit, which are derived from a single‐chain precursor by endoproteolytic processing. The precursor is not proteolytically processed in LoVo colon carcinoma cells. The uncleaved receptor immunopurified from the cells was cleaved in vitro by furin. Furthermore, the HGF/SF receptor was proteolytically processed in LoVo cells transfected with furin cDNA. These results indicate that furin is a processing endoprotease for the HGF/SF receptor. Tyrosine autophosphorylation of the uncleaved receptor was induced by HGF/SF, and the growth of the cells expressing the uncleaved receptor was stimulated by HGF/SF, indicating that the proteolytic processing of the receptor is not essential for the signal transduction of HGF/SF.

Calvete, Juan J.; Muñiz-Diaz, Eduardo

doi: 10.1016/0014-5793(93)80959-Xpmid: 7688323

The human alloantigen system Bak a/b is associated with a Ile 843→ Ser replacement on platelet glycoprotein IIb, the α‐subunit of the integrin receptor for fibrinogen (GPIIb/IIIa). Recent immunological studies indicate that sialylated oligosaccharide chain(s) are also implicated in expression of the Baka determinant. Here we show that the GPIIb fragment 704–856 contains the whole Bak a epitope, and that chemical cleavage of a single O‐linked oligosaccharide chain within this GPIIb domain correlates with the loss of its anti‐Baka antibodies binding ability. Ser847 was identified as the O‐glycosylation site. Therefore, our results show that the Ser847 modification is responsible for the expression of the GPIIb‐specific Baka alloantigen, and provide thus a link between the molecular biology and the immunologie observations.

Heinisch, Jürgen J.

doi: 10.1016/0014-5793(93)80960-3pmid: 8344431

Genes encoding phosphofructokinases (PFK) from Escherichia coli and from the human muscle were expressed in PFK‐deficient strains of Saccharomyces cerevisiae under the control of an inducible GAL1 promoter. They restored PFK activity under inducing conditions and complemented the galactose‐negative growth phenotype of the recipient strains. The PFK enzymes expressed appear to be stable in yeast. The human muscle enzyme crossreacts with specific antibodies and shows the expected subunit size. As expected, its activity can be activated by fructose‐2,6‐bisphosphate, in contrast to the bacterial enzyme.