SVIBOR - Project code: 1-07-073

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

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Project code: 1-07-073


CONTRIBUTION TO THE GLYCOSPHINGOLIPID METABOLISM


Main researcher: MESARIĆ, MARKO (30466)



Assistants
Type of research: basic
Duration from: 01/01/91. to 12/31/94.

Papers on project (total): 10
Papers on project quoted in Current Contents: 3
Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: Department of Chemistry and Biochemistry
Address: Šalata 3
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)1 45 66 752
Fax: 385 (0)1 42 40 01

Summary: Glycosphingolipids have long been associated with cell surface phenomena relevant to signal transduction. They are found primarily on the external leaflet of the plasma membrane, affect properties of cell surface receptors, and serve as the receptors, undergo changes with cell growth, differentiation, and neoplastic transformations, bind lectins, participate in cell-cell communication and cell-substratum interactions, serve as cell surface antigens, and alter the behaviour of cellular protein kinases. This project focuses on two directions: (*) Changes in the total content as well as glycosphingolipid composition of human lung, kidney, and adrenal gland during prenatal development. One general conclusion from our developmental data is that there are similarity in the glycosphingolipid composition during early differentiation (up to 22 weeks) with the data obtained for tumor tissues. (**) To investigate the mechanisms participating in the ganglioside biosynthesis the response of the enzymes sialyltransferase I (SAT I) and sialyltransferase II (SAT II) to sex steroid hormones (testosterone, progesterone, and á-estradiol) have been measured in rat kidney Golgi apparatus. Testosterone (10 mg / 0.1 ml DMSO) increased total content of gangliosides, as well as relative ratio of GD3 ganglioside, and decreased relative ratio of GM3 ganglioside. Testosterone increased the activity of SAT II. The mixture of á-estradio and progesterone (1:2000) increased the activity of SAT I but not of SAT II in castrated rat kidney.

Keywords: gangliosides, neutral glycosphingolipids, sialoglycoproteins, lung, kidney, adrenal gland, human prenatal development, sialyltransferase I (SAT I), sialyltransferase II (SAT II), testosterone, progesterone, á-estradiol, Golgi apparatus, rat kidney

Research goals: Glyosphingolipids are present in the plasma membrane of a great number of cell types. Studies of many laboratories indicate that these compounds play an important role in growth control and in the social behaviour of cells during differentiation, development and oncogenic transformation. In contrast to the experimental knowledge about glycosphingolipids there are few studies describing glycosphingolipid in the human fetal organs. First we collected the material, and today we have collection of tissues from 16th week of the gestation to the birth. Recently we investigated changes in the composition of the glycosphingolipids from human fetal liver during prenatal development. The purpose of our research is to observe the changes in the pattern of the glycosphingolipids from the human lung, kidney, and adrenal gland during prenatal development in normal as well as in pathological conditions, and compare it with the results from the adult organs. Previous studies on the age and sex dependency of the ganglioside patterns in rat liver in vivo and the concomitant determination of the activities of some enzymes involved in these pathways revealed the prominent role of the sialylation of GM3 to GD3 in determining the flow to the mono (a)- and polysialo (b)-series, respectively. Here, the influence of sex steroid hormones (testosterone, progesterone, and á-estradiol) on the total content and pattern of gangliosides, as well as on the activities of sialyltransferase I (SAT I) and sialyltransferase II (SAT II) in rat kidney will be studied.

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Last update: 10/09/95
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