Proflavine as a differential probe of gene expression: Inhibition of glutamine synthetase induction in embryonic retina☆

[摘要] Proflavine(3,6-diaminoacridine)wasshowntobeaneffectivemolecularprobeforanalysisofatissue-specificgeneexpressioninembryonicneuralretinacells.Theinductionbyhydrocortisoneofglutaminesynthetase(GS),amarkerofdifferentiationinthedevelopingretina,isdifferentiallyandreversiblyblockedbyproflavine.ConcentrationsofproflavinethattotallyinhibitthesynthesisofenzymaticallyandimmunologicallyreactiveGSonlyminimallyreducetotalRNAandproteinsynthesis.Proflavinedoesnothindertheuptakeofsteroidinducerintoretinacellsanditsbindingtocytoplasmicreceptors;nordoesitdirectlypreventthetranslationofGSmRNA.Theevidencesuggeststhatproflavinehinders,reversiblyanddifferentially,processesnecessaryfortheprovisionoffunctionaltranscriptsforGSsynthesis.ReplicationofDNAisnotrequiredforthereversibleinhibitionbyproflavineofGSsynthesis;norissuppressionofDNAsynthesisbyproflavinecausallyinvolvedinitseffectonGS.Thus,proflavinefunctionsinthiscaseasanonmutagenic,differentialmodifierofgeneexpression.Structuralfeaturesoftheproflavinemoleculeandrelatedderivativesrelevanttothiseffecthavebeendetermined.Theresultswarrantfurtherexplorationofproflavineandrelatedmoleculesasprobesofspecificgeneexpressioninthisandothersystems.

[学科分类] 生物科学（综合）