TYRPHOSTIN A9 AND WORTMANNIN PERTURB THE GOLGI-COMPLEX AND BLOCK PROLIFERATION OF VASCULAR SMOOTH-MUSCLE CELLS

Authors
Citation
J. Thyberg, TYRPHOSTIN A9 AND WORTMANNIN PERTURB THE GOLGI-COMPLEX AND BLOCK PROLIFERATION OF VASCULAR SMOOTH-MUSCLE CELLS, European journal of cell biology, 76(1), 1998, pp. 33-42
Citations number
41
Categorie Soggetti
Cell Biology
ISSN journal
01719335
Volume
76
Issue
1
Year of publication
1998
Pages
33 - 42
Database
ISI
SICI code
0171-9335(1998)76:1<33:TAAWPT>2.0.ZU;2-A
Abstract
To proliferate, vascular smooth muscle cells first convert from a cont ractile to a synthetic phenotype, Earlier studies indicate that this p rocess is supported by fibronectin and accelerated by platelet-derived growth factor (PDGF), Here, the mechanisms in this transition were fu rther explored. Isolated rat aortic smooth muscle cells were treated w ith tyrphostin A9, a PDGF receptor tyrosine kinase inhibitor, and wort mannin, a phosphoinositide 3-kinase inhibitor. Electron microscopy did not show any effect on the reorganization of the cells during the fir st days in culture, i.e. the loss of actin filaments and the formation of a large secretory apparatus. Conversely, both drugs caused hypertr ophy of the Golgi complex, with large and partly vacuolized cisternal stacks. Nevertheless, a juxtanuclear staining pattern for the Golgi en zyme mannosidase II, the coat protein beta-COP, and the PDGF beta-rece ptor was retained. Moreover, the serum-induced proliferation of the ce lls was blocked. These findings suggest that signaling via PDGF recept or tyrosine kinases and phosphoinositide 3-kinases is not necessary fo r the shift of the smooth muscle cells from a contractile to a synthet ic phenotype, On the other hand, these enzymes apparently carry out im portant functions in the control of intracellular membrane traffic and cell division.