Phenotype modulation in primary cultures of rat aortic smooth muscle cells. Effects of drugs that interfere with the functions of the vacuolar system and the cytoskeleton.
The transition of adult rat aortic smooth muscle cells from a contractile to a synthetic phenotype during the first week of primary culture on a substrate of fibronectin in serum-free medium was studied by light and electron microscopy. The weak base chloroquine and the carboxylic ionophore monensin were both found to inhibit the spreading of the cells and the accompanying changes in cellular fine structure. The exchange of myofilament bundles for a prominent rough endoplasmic reticulum and Golgi complex was delayed and vacuoles filled with incompetely degraded material accumulated in the cytoplasm. The microtubule-disruptive drugs colchicine and nocodazole likewise opposed the spreading and fine structural reorganization of the cells. Most typically, the Golgi stacks were small and widely dispersed. In addition, vacuoles of the type mentioned above increased in number. On the other hand, there was surprisingly little effect of cytochalasin B, a drug that is supposed to interfere with the assembly of actin filaments. The observations suggest that the phenotypic modulation of arterial smooth muscle cells is dependent on: (a) lysosomal degradation of discarded cellular constituents, (b) active vesicular transport along the exocytic pathway to provide the expanding cell surface with new membrane, and (c) a normal microtubular cytoskeleton to ensure the establishment of a new and functionally efficient intracellular organization.
Thyberg
J
J
Department of Medical Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Blomgren
K
K
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure*; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology*; D008297:Male; D008870:Microtubules / Q000502:physiology*; D008985:Monensin / Q000494:pharmacology; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains
D003572:Cytochalasins; C031582:cytochalasin C; D002738:Chloroquine; D008985:Monensin; D015739:Nocodazole; D003078:Colchicine