Iimveliso

Iimpembelelo ze-detergents kwi-P-glycoprotein umsebenzi we-atpase: ukungafani kokuphazamiseka kwemisebenzi exhomekeke kwi-basal kunye ne-verapamil.

I-P-glycoprotein (i-P-gp), i-membrane ye-plasma ye-glycoprotein ehambelana ne-phenotype yokumelana ne-multidrug, ijongene ne-ATP-dependent efflux yamachiza ahlukeneyo e-amphiphilic.Ukusebenzisa i-membrane vesicles elungiselelwe ukusuka kwi-multidrug resistant cell line DC-3F / ADX, sifunde ukuphazamiseka kwe-basal (okt ngokungabikho kweyeza) kunye ne-verapamil exhomekeke kwi-P-gp imisebenzi ye-ATPase eyenziwa yi-detergents eyahlukeneyo, kwi-non-solubilizing, kunye nakwi-solubilizing, ukugxila.I-membrane ye-solubilization eqhubekayo kunye nokunyuka koxinzelelo lwe-detergent kwajongwa ngokusasazwa kokukhanya kunye novavanyo lwe-centrifugation.Kwiindawo zokucoca ezinganyibilikiyo, zonke izicoci ezivavanyiweyo ngaphandle kwe-DOC zenze uthintelo oluyinxenye lwe-P-gp ye-ATPase, engazange idityaniswe nobungakanani beentlobo ezahlukeneyo zokucoca ezivavanyiweyo ezifakwe kwiinwebu.Uhlalutyo lwe-verapamil-induced P-gp activation lubonisa ukuba umsebenzi we-P-gp ATPase ulungelelaniswa ngokwahlukileyo yi-detergents kwi-non-solubilizing concentrations.Ke, intsebenziswano ethile phakathi kwe-P-gp kunye neesepha kunokwenzeka ukuba yenzeke kunokuba kuphazamiseke inwebu yehlabathi.Emva kwe-solubilization yi-detergents eyahlukeneyo evavanyiweyo, i-basal P-gp umsebenzi we-ATPase yayithintelwe ngokupheleleyo, ngaphandle kobukho be-CHAPS ekwazile ukugcina lo msebenzi kwinqanaba elithelekisekayo nelilinganiswa kwiinwebu zomthonyama.Nangona kunjalo, i-verapamil-induced P-gp ATPase activation yalahleka ngexesha le-P-gp solubilization yi-CHAPS, kodwa yachacha emva kokuhlanjululwa kwe-CHAPS ngaphantsi koxinzelelo lwe-micellar.Olu qwalaselo lubonisa ukusebenzisana okuthe ngqo phakathi kwe-P-gp kunye ne-CHAPS molekyuli ngaphakathi kwee-micelles ezixubeneyo.Ngokubanzi, idatha yethu engqina intsebenziswano ethile ye-P-gp / i-detergents iyahambelana nendawo yeendawo zokuthutha iziyobisi kwi-P-gp transmembrane domains.