Teratogens induce a subset of small heat shock proteins in Drosophila primary embryonic cell cultures.
Drosophila embryonic cells placed into culture just after gastrulation differentiate in vitro over the next 24 hr. A number of drugs that are teratogenic in mammalian systems have been found to inhibit muscle or neuron differentiation (or both) in these developing cultures. We have examined, by two-dimensional gel electrophoresis, the effects of these drugs on protein synthesis in embryonic cells. For nine teratogens tested, cells treated for 20 hr with the drug show a dramatic induction of three proteins of about 20 kilodaltons, in addition to the normal proteins synthesized by untreated cells. Three teratogens as well as all eight nonteratogens tested did not show this induction. The induced proteins appear to be identical to three of the heat shock proteins (hsp 23, 22a, and 22b), as shown by electrophoretic mobilities and peptide mapping by partial proteolysis. A 37 degrees C heat shock of the embryonic cells produces the full complement of heat shock proteins, whereas drug-treated cells induce only the subset hsp 23, 22a, and 22b but not hsp 26 or 27. beta-Ecdysterone, the Drosophila molting hormone, also inhibits embryonic differentiation and induces hsp 23, 22a, and 22b, a partial subset of the heat shock proteins (hsp 22, 23, 26, and 27) induced by the hormone in imaginal discs and some Drosophila continuous cell lines. Dose-response studies of several drugs show a correlation between the degree of inhibition of differentiation and the level of induction of hsp 23, 22a, and 22b. The induction of heat shock proteins by drugs may reflect specific types of stress that can also give rise to teratogenesis.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004330:Drosophila / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000502:physiology; D005775:Gastrula / Q000187:drug effects / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D008970:Molecular Weight; D013329:Structure-Activity Relationship; D013723:Teratogens / Q000633:toxicity*
D006360:Heat-Shock Proteins; D013723:Teratogens