Detail of "121706-11-4"

Reference

Structural requirements of lyngbyatoxin A for activation and downregulation of protein kinase C

Structural requirements of lyngbyatoxin A for activation and downregulation of protein kinase C.Some chemicals with cas registry numbers like 9026-43-1 and 121706-11-4 are also used. Basu, Alakananda; Kozikowski, Alan P.; Lazo, John S. (Sch. Med., Univ. Pittsburgh, Pittsburgh, PA 15261, USA). Biochemistry, 31(15), 3824-30 (English) 1992. CODEN: BICHAW. ISSN: 0006-2960. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Structure-activity studies of novel synthetic analogs of lyngbyatoxin A (I) reveal that the lactam ring but not the 7-linalyl moiety of I is essential for the in vitro stimulation of protein kinase C (PKC). (-)-Indolactam V (ILV), which contains no hydrophobic substituent at C-7, or analogs contg. either a linalyl or n-hexyl group at C-7 were equally efficacious in stimulating HeLa cell PKC in vitro and in competing with phorbol 12,13-dibutyrate for binding to PKC in intact cells. The hydrophobicity of alkyl groups at C-7, however, influenced the potency of these compds. to bind to and activate PKC. In addn., these compds. exhibited differences in their ability to translocate PKC. I (0.1 mM) like TPA induced a rapid translocation of PKC from the cytosol to the membrane and subsequently led to a sustained decrease in both cytosolic and membrane PKC activity. In contrast, (-)-n-hexylILV (0.1 mM) and (-)-ILV (1 mM) produced a transient and attenuated decrease in cytosolic PKC activity. At concns. that produced half-maximal PKC stimulation, (-)-ILV did not cause any downregulation of PKC whereas I and (-)-n-hexylILV led to 60% and 40% PKC downregulation, resp. Western blot analyses with monoclonal antibodies to PKC isoforms indicated that redn. in PKC activity by chronic exposure to TPA or I analogs could be explained by downregulation of PKCa. Constitutive expression of PKCb and PKCg isoforms was low in HeLa cells and was not affected significantly by TPA or I analogs. These results indicate that the structural requirements for PKC activation may be sepd. from those required for PKC downregulation. .