Cov neeg thauj khoom thiab lawv cov luag haujlwm hauv chaw muag tshuaj

Cov neeg thauj khoom thiab lawv lub luag haujlwm

Cov neeg thauj khoom yog cov chav kawm dav dav ntawm transmembrane uas spor cell membrane uas muaj ntau lub ntsej muag thiab ua si ib txwm muaj nyob hauv tus kab mob) thiab exogenous (txawv teb chaws) cov tshuaj. Cov tshuaj loog no ua ke ua molecular tus thawj coj mus tswj hwm lub cell thiab cov tshuaj hormones Nyob rau hauv cov ntsiab lus ntawm cov chaw muag tshuaj, "cov neeg thauj khoom" feem ntau xa mus rau cov protein uas siv tshwj xeeb cov txheej txheem kom txav kho cov kev siv hluav taws xob thoob plaws. Ob lub tsev neeg loj ua tus txheej txheem no: ATP - Cov Cassette (ABC) superfamily thiab solute cabramily thiab solute cabramily thiab solutab) superfamily.

ABC thauj neeg: ATP - Tsav Chaw Tove

ABC thauj neeg yog thawj lub zog thauj neeg uas muaj zog los ntawm ATP Hydrolysis los txav ntau yam ntawm cov membanes cellular, txawm tias muaj kev cuam tshuam ntawm cellular class. Lub cim ntawm cov thauj khoom no yog lawv cov khoom lag luam zoo heev - Lawv lub zog - Nquag muaj nuj nqi tsis yog rau kev tswj hwm ntawm lub tsev pheeb suab ntawm lub tsev pheebsab thiab tseem ua rau kev siv tshuaj yeeb. Piv txwv li, los ntawm nquag effluxing kws kho mob cov tshuaj tiv thaiv kab mob qog noj ntshav, lawv txo cov tshuaj tiv thaiv kab mob hauv cov tshuaj thiab ua rau multidrug Kuj (MRDR coj).

SLC thauj neeg: Kev siv lub tshuab thiab theem nrab lub zog

Nyob rau hauv kev sib piv rau ABC thauj neeg, cov tswv cuab ntawm solute cabrier (slc) superfamily feem ntau tsis xav tau ncaj qha ATP Hydrolysis. Hloov chaw, cov neeg thauj khoom qeeb qeeb ua haujlwm feem ntau raws li cov khoom thauj theem nrab nquag lossis cov neeg thauj khoom. Lawv siv tau preexisting classochemical electrients-feem ntau tsim los ntawm ion twj-kom tsav cov dej qab zib lossis cov amurotransmitters, thiab ntau yam organic ions. Ntau cov tshuaj uas muaj hydrophilic lossis nthuav tawm cov khoom lag luam qis qis dua rau cov neeg thauj mus los ntawm cov haujlwm cellular thiab tom ntej. Vim tias lawv tau tsav los ntawm ion gradients feem ntau muab cov kev tswj hwm zoo tshaj plaws substrate thiab kev coj ua uas yog qhov tseem ceeb rau kev ua haujlwm ntawm lub cev thiab chaw muag tshuaj.

Tshuaj EFFLUX tiv thaiv cov dej num tshwj xeeb: kev ua haujlwm tshwj xeeb

Hauv cov txheej txheem kev thauj khoom tag nrho ntawm cov tshuaj thauj, qee cov neeg thauj tau tshwj xeeb rau cov tshuaj efflux, thaum lwm tus muab tshuaj yeeb. Cov neeg thauj khoom efflux, feem ntau yog los ntawm ABC tsev neeg, siv ATP Hydrolysis kom nquag tshem tawm cov tebchaw ntawm cov hlwb. Qhov haujlwm no tseem ceeb heev rau kev poob siab nqus ntawm cov nqaij ntswg thiab rau kev tiv thaiv cov plab hnyuv siab raum. Uptake cov neeg thauj, feem ntau nyob rau hauv tsev neeg SLC, xa cov tshuaj thiab endogenous molecules rau hauv cov hlwb, ua rau lawv lub chaw ua noj ntawm cov chaw pharmachology. Ua ke, kev sib koom ua ke ntawm efflux thiab uptake cov neeg thauj mus los txiav txim siab ntshav, yog li cuam tshuam, yog li cuam tshuam kev ua tau zoo thiab lom.

Cov Neeg Thauj Khoom thiab Lawv Tes Haujlwm

MDR1 (p - glycoprotein, abcb1)

Raws li ib qho ntawm feem ntau dav tau kawm ABC thauj neeg, MDR1 (feem ntau paub txog P - GP) yog feem ntau ntawm cov nqaij mos xws li, mob siab, thiab ntshav lub hlwb (bbb). Los ntawm nquag siv cov tshuaj thiab xenobiiSics tawm ntawm cov hlwb, p - GP txwv qhov ncauj tshuaj thiab ua kom muaj kev tshem tawm sai sai. Clinically, kev tshaj tawm ntawm p - GP hauv cov qog yog ib qho kev sib tw uas yuav tsum tau siv cov kev siv tshuaj lossis cov kev sib tw ntawm cov chresssensitizers uas inhibit nws muaj nuj nqi. P - GP lub peev xwm los thauj cov khoom siv dav dav ntawm cov neeg tsis sib haum xeeb-los ntawm Anticancer cov tshuaj pleev-los ntawm Anticikoticology thiab Tshuaj Tiv Thaiv Kev Tiv Thaiv Kev Tiv Thaiv thiab Tshuaj Kho Mob.

BSEP (Bile SALP EXPORP TWJ, ABCB11)

BSEP yog daim siab - SPECIAPLY ABC Transporter uas yog qhov tseem ceeb rau kev tso zais zais ntawm bile acids los ntawm Hepatocytes rau hauv Bile Canaliculi. Cov txheej txheem no yog qhov tseem ceeb rau kev zom thiab nqus ntawm kev noj haus cov rog thiab rau kev tswj cov kua txiv aub lub tsev pheebsasis. Kev cuam tshuam ntawm BSP muaj nuj nqi - txawm siv tshuaj yeeb los yog tshuaj tsis muaj kev sib cav sib ceg - tuaj yeem ua rau cholestasis, ib qho xwm txheej los ntawm cov khoom noj tsis zoo. Kev Mob Siab Hlwb Kev Mob Siab Loj Yuav ua kom muaj kev ua kom muaj tshuaj phem rau cov tshuaj Hepatotoxic thiab rau kev txhim kho kev kho mob los kho cov mob colaceutatic.

BRRP (tus mob cancer mis protein, abcg2)

BRRP yog lwm qhov ATP - Rependx Transporter uas tau nthuav dav hauv cov nqaij mos xws li placenta, mob siab, thiab cov ntshav-lub hlwb. Nyob rau hauv cov ntsiab lus ntawm cov tshuaj pov tseg, brrp txwv qhov system tshwm sim ntawm kev kho cov tshuaj tiv thaiv thiab cov tshuaj tua kab mob, los ntawm kev tso lawv tawm ntawm cov hlwb. Nws txoj kev xaiv lub zos hauv zos hauv cov ntaub so ntswg muaj kev tiv thaiv tus me nyuam thiab lub hlwb los ntawm xenobiotics. Kev ua yeeb yam kev sib txawv lossis dysregulated kev qhia ntawm BRP tuaj yeem hloov cov tshuaj noj phom sij thiab tau cuam tshuam rau cov tshuaj kho mob thiab cov tshuaj muaj txiaj ntsig.

Mate1 / Mate2 - k (multidrug thiab toxin excusion proteins)

Cov thauj khoom no yog ib feem ntawm SLC superfamily thiab yog feem ntau qhia nyob rau hauv lub raum thiab hepatic cov nqaij. Mate1 thiab MATE2] K Ua haujlwm ua ke nrog cov basolaterally nyob organic cation thauj neeg (OctCAr) kom haum rau cov tshuaj thiab cov co toxins. Los ntawm extruding cationic substrates rau hauv cov zis lossis bile, cov proteins no pab tswj cov tshuaj tshem tawm thiab txo cov tshuaj lom neeg kom tsawg. Lawv txoj kev ncaj ncees yog qhov tseem ceeb rau kev tiv thaiv kev sib tw tshuaj, uas tuaj yeem ua rau muaj kev sib raug zoo nrog rau Neptotoxicity.

OATP1B1 (organic anion thauj cov polypeptide 1b1, SERCO1B1)

Tseem ceeb tshaj plaws rau ntawm Sinusoidal membrane ntawm Hepatoidal, OATP1B1 yog tus yuam sij ntawm ntau lub luag haujlwm rau kev mob siab, tshuaj tua kab mob, thiab anticancer cov neeg sawv cev. Cov transporter no tseem ua lub luag haujlwm tseem ceeb nyob rau hauv lub uptake ntawm endogenous compound xws li bilirubin, steroid conjugates, thiab cov thyroid hormones. Cov variants hauv SLRO1b1 gene muaj peev xwm cuam tshuam ntau rau cov tshuaj siv tshuaj yeeb, piv txwv, los ntawm kev hloov pauv ntawm statins thiab nce kev pheej hmoo ntawm myopathy. Yog li, OATP1B1 yog qhov tseem ceeb hauv chaw muag tshuaj thiab tshuaj kho mob.

OAT1 (organic anion Transporter 1, SLC22A6)

Oat1 feem ntau yog qhia txog Basolateral membrane ntawm lub raum thuam thiab lub luag haujlwm ntawm cov organic ntawm cov organic organic ntawm cov hlab ntshav. Cov txheej txheem no tsis yog tsuas yog tso zis rau endabolites-xws li tso zis zoo li cov tshuaj tua kab mob - tab sis kuj siv tshuaj tua kab mob (NSAIDS), thiab cov co toxins. Kev hloov pauv hauv OAT1 muaj nuj nqi lossis kev hais tawm tuaj yeem cuam tshuam cov tshuaj porpardots thiab ua rau cov tshuaj - induced neproxicity. Tus Transporter lub luag haujlwm hauv lub luag haujlwm hauv lub raum ua rau nws yog ib tus cim tseem ceeb rau kev twv tshuaj thiab tswj cov tshuaj tiv thaiv kev phiv tshuaj thiab tswj hwm cov tshuaj tiv thaiv thiab tswj tau cov tshuaj tiv thaiv kab mob thiab tswj hwm cov tshuaj tiv thaiv mob npaws.

Ntsiab lus thiab cov chaw kuaj mob cuam tshuam

Ua ke, cov neeg thauj khoom no tau ua haujlwm ntawm kev nqus, kev faib tawm, cov metabolism, thiab kev lees paub (kev lees paub) yog qhov tseem ceeb rau cov chaw muag tshuaj. Lawv txoj kev ua ke tsis yog tsuas cuam tshuam rau kev ua tau zoo thiab tshuaj lom neeg ua haujlwm thiab tsis muaj kev sib txuas lus tsis zoo thiab muaj kev sib txuas lus. Hauv kev siv tshuaj, nkag siab txog cov yam ntxwv ua haujlwm thiab cov cwj pwm muaj zog ntawm cov thauj khoom no yog qhov tseem ceeb. Nws pab ua kev kwv yees tshuaj - Cov tshuaj sib cuam tshuam, kev kho mob ntawm kev kho mob, thiab kev cuam tshuam zoo. Cov kws tshawb nrhiav thiab cov kws kho mob tsis tu ncua cov ncauj lus kom tsis txhob sib tw, ua rau muaj kev nyuaj siab xws li multidrug tsis taus thiab tshuaj kho mob lossis mob raum.

Cov Ntsiab Lus: ATP - Cov Cassette (ABC), ABC Transple, MRCK), MRCK) Kev tshawb fawb, Hek293 Mock, thuam SLC Transporter