S100 proteins yog ib tsev neeg uas tsis tshua muaj molecular hnyav cov ntaub so ntswg tshwj xeeb calcium-binding proteins nrog ib tug modulatory nyhuv uas muaj feem xyuam rau ntau yam physiological dab nyob rau hauv lub cev. Lub npe characterizes lub peev xwm ntawm cov tebchaw ntawm cov pab pawg no kom yaj tag rau hauv 100% ammonium sulfate tov ntawm nruab nrab pH qhov tseem ceeb.
Tam sim no, 25 tus neeg sawv cev ntawm tsev neeg no paub, uas yog cov yam ntxwv ntawm cov ntaub so ntswg sib txawv. Qhov no qhia tau hais tias lub hlwb tshwj xeeb s100 proteins yog cov proteins uas muaj nyob rau hauv lub hlwb hlwb thiab koom nrog cov txheej txheem neurophysiological.
Discovery keeb kwm
thawj s100 protein tau raug cais tawm hauv xyoo 1965 los ntawm lub hlwb bovine los ntawm cov kws tshawb fawb Moore thiab Gregor. Tom qab ntawd, cov proteins ntawm tsev neeg no tau pom nyob rau hauv cov tsiaj nyeg, noog, tsiaj reptiles, thiab tib neeg. Thaum pib, nws tau xav tias s100 tsuas yog nyob rau hauv cov ntaub so ntswg, tab sis nrog kev txhim kho ntawm kev tiv thaiv kab mob, cov proteins ntawm pab pawg no tau pib pom nyob rau hauv lwm yam kabmob.
Cov yam ntxwv dav dav thiab thaj chaw
Proteins ntawm s100 tsev neeg tsuas muaj nyob rau hauv vertebrates thiab tib neeg. Ntawm 25 cov proteins hauv pawg no, 15 yog lub hlwb tshwj xeeb, feem ntau yog tsim los ntawm cov hlwb astroglial hauv CNS, tab sis qee qhov kuj muaj nyob hauv cov neurons.
Nws tau raug tsim los tias 90% ntawm tag nrho s100 feem hauv lub cev yog yaj nyob rau hauv cytoplasm ntawm cov hlwb, 0.5% yog nyob rau hauv lub nucleus thiab 5-7% yog txuam nrog daim nyias nyias. Ib feem me me ntawm cov protein tau pom nyob rau hauv qhov chaw extracellular, nrog rau cov ntshav thiab cov kua cerebrospinal.
Protein ntawm pawg s100 muaj nyob rau hauv ntau lub cev (tawv nqaij, daim siab, lub plawv, spleen, thiab lwm yam), tab sis nyob rau hauv lub hlwb nws yog ib puas txhiab zaus. Qhov siab tshaj plaws concentration yog pom nyob rau hauv lub cerebellum. Cov protein s100 kuj tseem ua haujlwm nyob rau hauv melanocytes (cov qog nqaij hlav ntawm daim tawv nqaij). Qhov no tau coj mus rau kev siv cov tshuaj no ua cov ntaub so ntswg ntawm ectodermal keeb kwm.
Tshuaj, s100 proteins yog dimers nrog ib qho hnyav molecular ntawm 10-12 d altons. Cov proteins no yog acidic vim tias lawv muaj ntau npaum li cas (txog 30%) ntawm glutamic thiab aspartic amino acid residues. Cov muaj pes tsawg leeg ntawm s100 molecules tsis suav nrog phosphates, carbohydrates thiab lipids. Cov proteins no tuaj yeem tiv taus kub txog 60 degrees.
Structure thiab spatial conformation
Cov qauv ntawm txhua tus tswv cuab ntawm s100 tsev neeg yog cov proteins uas muaj lub ntiaj teb. Cov muaj pes tsawg leeg ntawm ib dimeric molecule muaj xws li 2 polypeptides (alpha thiab beta), txuas rau ib leeg los ntawm non-covalent bonds.
Cov tswv cuab ntawm tsev neeg feem ntau yog homodimers tsim los ntawm ob lub subunits zoo tib yam, tab sis kuj muaj heterodimers. Txhua polypeptide nyob rau hauv s100 molecule muaj calcium-binding motif hu ua EF tes. Nws yog tsim raws li cov kauv-voj-kauv hom.
Cov s100 protein muaj 4 α-helical ntu, thaj tsam hauv nruab nrab pob khawm ntawm qhov sib txawv ntawm qhov ntev, thiab ob lub davhlau ya nyob twg sib txawv (N thiab C).
Txoj Kev Ua Haujlwm
S100 proteins lawv tus kheej tsis muaj kev ua haujlwm enzymatic. Lawv txoj haujlwm yog ua raws li kev sib txuas ntawm calcium ions, uas koom nrog ntau cov txheej txheem intercellular thiab intracellular, nrog rau cov teeb liab. Qhov sib ntxiv ntawm Ca2+ rau s100 molecule ua rau nws spatial rearrangement thiab qhib lub hom phiaj protein-binding chaw, los ntawm kev cuam tshuam nrog Lwm cov proteins yog nqa tawm.
Yog li, s100 tsis yog cov proteins uas nws lub luag haujlwm tseem ceeb yog tswj cov concentration ntawm Ca2+. Proteins ntawm pab pawg no yog cov teeb liab-hloov pauv calcium-raws li kev ua haujlwm lom neeg lom zem modulators uas cuam tshuam rau cov txheej txheem intracellular thiab extracellular los ntawm kev khi rau lub hom phiaj cov protein. Neurotransmitters kuj tuaj yeem ua raws li qhov kawg, uas yog vim li cas rau kev cuam tshuam ntawm s100 ntawm kev xa cov paj hlwb.
Tam sim no, nws tau tshaj tawm tias zinc thiab / lossis tooj liab ions ua raws li kev tswj hwm rau qee qhov s100 es tsis yog Ca2+. Qhov sib ntxiv ntawm qhov kawg tuaj yeem cuam tshuam ncaj qha rau kev ua haujlwm ntawm cov protein thiab hloov nws txoj kev sib raug zoo rau calcium.
Functions
Daim duab tiav ntawm lub luag haujlwm lom neeg ntawm lub hlwb tshwj xeeb s100 cov proteins hauv lub cev tseem tsis tau muaj. Txawm li cas los xij, kev koom tes ntawm cov protein ntawm pab pawg no hauv cov txheej txheem hauv qab no tau tshwm sim:
- kev tswj cov tshuaj tiv thaiv metabolic ntawm cov hlab ntsha paj hlwb;
- DNA replication;
- nthuav qhia cov ntaub ntawv caj ces;
- glial cell proliferation;
- tiv thaiv oxidative (oxygen-related) cell puas;
- sib txawv ntawm cov neurons tsis paub qab hau;
- kev tuag ntawm neurons los ntawm apoptosis;
- cytoskeleton dynamics;
- phosphorylation thiab secretion;
- kis ntawm lub paj hlwb impulse;
- kev cai ntawm lub voj voog ntawm tes.
Nyob ntawm hom thiab thaj chaw, lub paj hlwb tshwj xeeb s100 cov proteins tuaj yeem muaj ob qho tib si hauv cov cellular thiab extracellular. Cov nyhuv ntawm qee cov proteins yog qhov concentration nyob ntawm. Yog li, cov protein uas paub zoo s100B ntawm cov ntsiab lus ib txwm nthuav tawm cov haujlwm neurotrophic, thiab ntawm qib siab - neurotoxic.
Extracellular hlwb-specific s100 proteins tej zaum yuav koom nrog inflammatory teb, tswj glial thiab neuronal sib txawv, thiab ua rau apoptosis (programmed cell tuag). Qhov tseem ceeb ntawm s100 tau ua pov thawj hauv qhov kev sim hauv vitro uas cov neurons tsis muaj sia nyob yam tsis muajcov protein no.
Diagnostic value s100
Tus nqi kuaj mob ntawm s100 yog raws li kev sib raug zoo ntawm nws cov concentration hauv cov ntshav ntshav (lossis cov kua dej cerebrospinal) nrog CNS pathologies thiab kab mob oncological. Nws tau raug tsim los hais tias thaum cov hlwb glial puas lawm, cov protein no nkag mus rau qhov chaw extracellular, los ntawm qhov uas nws nkag mus rau hauv cov kua cerebrospinal thiab tom qab ntawd mus rau hauv cov ntshav. Yog li, raws li kev nce hauv qhov concentration ntawm s100 hauv cov ntshav, qhov kev txiav txim siab tuaj yeem rub tawm txog ntau lub hlwb pathologies. Kev sib raug zoo ntawm cov ntsiab lus ntawm cov protein no hauv cov ntshav thiab cov kab mob ntawm lub paj hlwb hauv nruab nrab tau raug kuaj pom tseeb.
txhawm rau ua kom cov concentration ntawm s100 hauv cov kua dej ntxiv ua rau tsis yog vim kev puas tsuaj ntawm cellular barriers synthesizing cov protein no. Thawj cov lus teb rau ntau lub hlwb pathologies yog lub npe hu ua glial teb, ib feem ntawm qhov kev siv ntawm s100 secretion los ntawm astrocytes. Kev nce hauv cov ntsiab lus ntawm cov protein no hauv cov ntshav kuj tseem qhia tau tias muaj kev ua txhaum ntawm cov ntshav-hlwb barrier.
Kev soj ntsuam qib ntawm s100 tso cai rau koj los ntsuas qib ntawm lub hlwb puas, uas yog qhov tseem ceeb hauv kev kuaj mob. Kev txheeb xyuas kev sib raug zoo ntawm tus nqi ntawm cov protein no thiab neuropathology zoo ib yam li kev sib raug zoo ntawm cov concentration ntawm c-reactive protein nrog cov kab mob hauv lub cev.
Siv raws li qog nqaij hlav
Cov s100 protein tau pib siv los ua cov qog nqaij hlav thaum ntxov 1980s. Tam sim no, txoj kev no zoo rau kev tshawb pom ntxov ntawm mob qog noj ntshav, rov tshwm sim lossis metastasis. Feem ntau s100 yog siv hauvKev kuaj mob melanoma lossis neuroblastoma.
Nws yog ib qho tsim nyog yuav tsum paub qhov txawv ntawm thaum twg cov protein no raug tshuaj xyuas kom kuaj pom CNS pathologies lossis lwm yam kab mob, thiab thaum twg nws siv los kuaj mob qog noj ntshav. Yog tias qhov kev taw qhia tshwj xeeb mus rau tus neeg saib xyuas, kev txiav txim siab ntawm s100 protein yuav tsum tau coj mus rau hauv tus account lwm yam laj thawj rau qhov nce hauv cov concentration ntawm cov tshuaj ntsuam xyuas hauv cov ntshav. Thaum txhais cov txiaj ntsig, nco ntsoov ua tib zoo saib rau txoj kev tsom xam, txij li thaj tsam ntawm qhov kev siv lub sijhawm (cov ntsuas ib txwm muaj) nyob ntawm nws.
Qhov tsis zoo ntawm tus cim s100 yog nws qhov kev xaiv qis, vim tias qhov nce ntawm cov protein ntau hauv cov ntshav thiab CSF tuaj yeem cuam tshuam nrog ntau yam pathologies, tsis tas yuav muaj mob qog noj ntshav. Yog li, s100 protein tsis tuaj yeem muab tus nqi txiav txim siab. Txawm li cas los xij, cov protein no tau ua pov thawj nws tus kheej ua tus cim mob qog noj ntshav.
Presence level in blood serum
Nquag, s100 protein yuav tsum muaj nyob hauv cov ntshav hauv qhov tsawg dua 0.105 µg / l. Tus nqi no sib haum mus rau qhov txwv siab tshaj ntawm cov concentration hauv tus neeg noj qab haus huv. Tshaj li qib tso cai (DL) s100 yuav qhia tau tias:
- CP;
- mob hlwb;
- kev txhim kho ntawm malignant melanoma (los yog nws rov tshwm sim);
- xeeb tub;
- neuroblastoma;
- dermatomyositis;
- npog thaj chaw loj ntawm qhov kub hnyiab.
Protein qib kuj tuaj yeem nce ntxiv nrog kev ntxhov siab lossis kev raug mob ntevlub cev nyob rau hauv cheeb tsam ultraviolet. Qhov concentration hauv cov ntshav yog txiav txim siab los ntawm kev tshuaj xyuas tsim nyog.
Kev kuaj pom hauv lub cev
Muaj ntau txoj hauv kev los kuaj pom muaj s100 hauv cov ntshav, suav nrog:
- immunoradiometric assay (IRMA);
- mass spectroscopy;
- western blot;
- YELISA (enzyme immunoassay);
- electrochemiluminescence;
- quantitative PCR.
Txhua yam ntawm cov kev tshuaj ntsuam no yog qhov muaj txiaj ntsig zoo thiab tso cai rau kev txiav txim siab ntau ntawm cov ntsiab lus ntawm s100. Txij li thaum cov protein no muaj lub neej luv luv (30 feeb), cov ntshav ntshav siab tsuas yog ua tau nrog cov khoom noj tas li los ntawm cov ntaub so ntswg.
Hauv kev kuaj mob, ib qho kev siv hluav taws xob electrochemiluminescent immunoassay rau s100 protein feem ntau yog siv. Txoj kev tshawb no ua ke siv cov tshuaj tiv thaiv kab mob rau cov protein uas pom tau tias muaj teeb pom kev zoo. Cov cuab yeej txiav txim siab qhov concentration s100 los ntawm kev siv hluav taws xob chemiluminescent.
Antibodies rau protein s100
Hauv tshuaj, cov tshuaj tiv thaiv rau s100 protein muaj 2 thaj chaw ntawm kev siv tswv yim:
- kuaj mob - siv hauv kev tiv thaiv kab mob txhawm rau txheeb xyuas qhov concentration ntawm cov protein no hauv cov ntshav los yog CSF (qhov no, s100 yog ib qho antigen);
- kho mob - kev taw qhia cov tshuaj tiv thaiv rau hauv lub cev yog siv los kho qee yam kab mob.
Antibodies siv lawv cov txiaj ntsig los ntawm kev hloov pauvcuam tshuam rau s100 proteins. Cov tshuaj muaj npe nrov ntawm lub hauv paus no yog Tenoten. Cov tshuaj tiv thaiv kab mob rau s100 muaj txiaj ntsig zoo rau lub paj hlwb, txhim kho kev sib kis. Tsis tas li ntawd, cov tshuaj no muaj peev xwm txwv tsis pub cov tsos mob tshwm sim ntawm kev tsis sib haum xeeb ntawm kev ua haujlwm autonomic hauv lub plab zom mov.
