Differential effects of ceramides upon adenylyl cyclase subtypes.
Ceramides are reported to stimulate different effector systems, among them atypical protein kinases C (PKCs). When HEK 293 cells, stably expressing adenylyl cyclase type II (AC II), were treated with various ceramide derivatives, adenylyl cyclase activity was enhanced 8-15-fold. The stimulation by the most potent analog, C18/C24 ceramide, was comparable to that by the phorbolester TPA. The stimulatory effect of ceramide was not restricted to AC II, although the type I and type V enzymes were affected less dramatically. Unexpectedly, the dihydro derivatives of ceramides, generally serving as non-activating controls, exhibited only slightly lower stimulation than ceramides, whereas short-chain ceramides (e.g. C2) were without effect. The action of ceramides was at least partially inhibited by okadaic acid, suggesting involvement of a phosphatase. Furthermore, ceramides and TPA operated synergistically. While the PKC inhibitor staurosporine counteracted the action of phorbol-esters, it significantly (2.5x) enhanced the effect of ceramides.
Bösel
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Department of Physiological Chemistry II, Heinrich-Heine-University, Düsseldorf, Germany.
Pfeuffer
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D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002518:Ceramides / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D002518:Ceramides; D007527:Isoenzymes; D011994:Recombinant Proteins; D000262:Adenylyl Cyclases