Effects of 12-O-tetradecanoyl-phorbol- 13-acetate on myofibril integrity and Ca2+ content in developing myotubes☆

[摘要] Thecocarcinogen12-O-tetradecanoyl-phorbol-13-acetate(TPA)hasapromptandselectiveeffectonstriatedmyofibrilsinwell-formed,multinucleatedmyotubes.Themyofibrillarapparatusistotallydisruptedandlargelydegradedafter3daysinTPA.Fluorescent-taggedantibodiestomuscle-specificlightmeromyosinandelectronmicroscopydocumentthiscataboliceffectofTPA.Thisselectivedegradationoffullyassembledstriatedmyofibrilsisreadilyreversible.Thisreassemblyofmyofibrilsrequiresdenovoproteinsynthesis.TheTPA-treatedmyotubesareunusuallyrichinautophagosomes,organellesrarelyobservedinnormalmyotubes.TPAhasnodiscernableeffectonthemorphologyofthesubsarcolemmalmicrofilaments,mitochondria,microtubules,orsarcoplasmicreticulum(SR).Theprogrammeddisappearanceofthefibroblast-type,intermediate10-nmfilaments(FIF)thatoccursasnormalmyotubesmatureisnotalteredbyTPA.However,theTPA-treatedmyotubesdepletedofmyofibrilsarefilledwithanextensivemeshworkofthemuscle-typeintermediate10-nmfilaments(MIF).Thedrughasnoobviouseffectontheconstitutivecontractileproteinscomprisingthesubmembranousmicrofilaments,ortheFIFinpresumptivemyoblastsorfibroblasts,nordoesitaffectthemotilityassociatedwiththesereplicatingcells.ThestrikingincreaseintotalcalciumcontentwhichoccursasnormalmyotubesmatureisabsentinmyotubestreatedwithTPA.

[学科分类] 生物科学（综合）