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
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.