S100B
S100 kalcij-vezujući protein B (S100B) jest član porodice S-100 proteina, koji je kod ljudi kodiran genom S100 sa hromosoma 21.
S100 proteini su nalaze se u citoplazmi i jedru širokog spektra ćelija i uključeni su u regulaciju brojnih ćelijskih procesa kao što su napredovanje ćelijskog ciklusa i ćelijska diferencijacija. S100 geni uključuju najmanje 13 članova koji su locirani kao klaster na hromosomskoj regiji 1q21; međutim, ovaj gen se nalazi na 21q22.3.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 92 aminokiseline, a molekulska težina 10.713 Da.
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MSELEKAMVA | LIDVFHQYSG | REGDKHKLKK | SELKELINNE | LSHFLEEIKE | ||||
| QEVVDKVMET | LDNDGDGECD | FQEFMAFVAM | VTTACHEFFE | HE |
Funkcija
urediS100B je specifičan za gliju, eksprimiran prvenstveno putem astrocita, ali ga ne eksprimiraju svi astrociti. Pokazalo se da se S100B eksprimira samo podtipom zrelih astrocita koji pokrivaju krvne sudove i u čelijama koje eksprimiraju NG2.[5]
Ovaj protein može funkcionirati u proširenju neurita, proliferaciji ćelija melanoma, stimulaciji tokova Ca2+, inhibiciji PKC posredovane fosforilacije, astrocitoza, proliferacija aksona i inhibicija sklapanja mikrotubula. U razvoju centralnog nervnog sistema (CNS) djeluje kao neurotrofni faktor i protein za preživljavanje neurona. U odraslom organizmu obično je na povišenoj razini zbog oštećenja nervnog sistema, što ga čini potencijalnim kliničkim markerom.
Klinički značaj
urediHromosomski preuređenje i izmijenjena ekspresije ovog gena su implicirani u nekoliko neuroloških, neoplazijskih i ostalih tipova bolesti, uključujući Alzheimerovu bolest, Downov sindrom, epilepsiju, amiotrofnu lateralnu sklerozu, švanom, melanom i dijabetes melitus tipa I.[6]
Sugerirano je da regulacija S100B pomoću melitina ima potencijal za liječenje epilepsije.[7]
Dijagnostička upotreba
urediS100B luče astrociti ili se može izliti iz ozlijeđenih ćelija i ući u vanćelijski prostor ili krvotok. Nivo S100B u serumu povećan je kod pacijenata tokom akutne faze oštećenja mozga. Tokom posljednje decenije, S100B se pojavio kao kandidat za periferni biomarker permeabilnosti krvno-moždane barijere (BBB) i povrede CNS-a. Povišeni nivoi S100B tačno odražavaju prisustvo neuropatoloških stanja uključujući traumatske povrede glave ili neurodegenerativne bolesti. Normalni nivoi S100B pouzdano isključuju velike patološke promjene CNS-a. Njegova potencijalna klinička upotreba u procesu donošenja terapijskih odluka potkrijepljena je ogromnom količinom literature koja potvrđuje varijacije u nivoima 100B u serumu sa standardnim modalitetima za prognozu obima oštećenja CNS-a: promjene u neurosnimcima, cerebrospinalnom pritisku i drugim molekulskim markerima mozga (neuronski specifična enolaza i glijski vlaknasti kiseli protein). Međutim, što je još važnije, zabilježeno je da se nivoi S100B povećavaju prije bilo kakvih uočljivih promjena unutarmoždanog peritiska, neurosnimanja i nalaza neurološkog skrininga. Dakle, glavna prednost upotrebe S100B je to što povišenje nivoa u serumu ili CSF-u pružaju osjetljivu mjeru za određivanje povrede CNS-a na molekulskm nivou prije nego što se razviju grube promjene, omogućavajući pravovremenu isporuku ključne medicinske intervencije prije nego što dođe do nepovratnog oštećenja. Prije napada, povišeni su nivoi S100B u serumu, što sugerira da bi curenje BBB moglo biti rani događaj u njegovom razvoju.[8]
Izuzetno važna primjena testiranja serumskog S100B je u odabiru pacijenata s lakšim ozljedama glave kojima nije potrebna daljnja neuroradiološka evaluacija, jer su studije koje su upoređivale CT skeniranje i nivoe S100B pokazale da su vrijednosti S100B ispod 0,12 ng/mL povezane s niskim rizikom očiglednih neuroradioloških promjena (kao što je intrakranijsko krvarenje ili oticanje mozga) ili značajnih kliničkih posljedica.[9] Odlična negativna prediktivna vrijednost S100B u nekoliko neuroloških stanja je zbog činjenice da serumski nivoi S100B odražavaju promjene permeabilnosti krvno-moždane barijere, čak i u odsustvu neuronske ozljede.[10][11] Osim toga, S100B, koji je također prisutan u ljudskim melanocitima, pouzdan je marker za zloćudnost melanoma, kako u biopsijskom tkivu tako i u serumu.[12][13]
Modelni organizmi
urediU proučavanju funkcije S100B korišteni su modelni organizmi. Uvjetna linija nokaut-miša, zvana S100btm1a(EUCOMM)Wtsi[14][15] generirana je kao dio Međunasrodnog konzorcija za nokaut-miševe— projekta mutageneze velike propusnosti za generiranje i distribuciju životinjskih modela bolesti zainteresovanim naučnicima — u Institutu Wellcome Trust Sanger.[16][17][18]
| Svojstvo | Fenotip |
|---|---|
| Vijabilnost homozigota | Normalan |
| Plodnost | Normalan |
| Tjelesna težina | Normalan |
| Anksioznost otvorenog polja | Normalan |
| Neurološka procjena | Normalan |
| Snaga stiska | Normalan |
| Test vruće ploče | Normalan |
| Dismorfologija | Normalan |
| Posredna kalorimetrija | Normalan |
| Test tolerancije glukoze | Normalan |
| Slušni odgovor moždanog stabla | Normalan |
| DEXA | Normalan |
| Radiografija | Normalan |
| Tjelesna temperatura | Normalan |
| Morfologija oka | Normalan |
| Klinička hemija | Normalan |
| Hematologija | Normalan |
| Limfociti periferne krvi | Normalan |
| Mikronukleus test | Normalan |
| Težina srca | Normal |
| Histopatologija mozga | Normalan |
| Salmonella infekcija | Normalan[19] |
| Citrobacter infekcija | Normalan[20] |
| Svi testovi i analize su prema:[21][22] |
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[21][23] Obavljena su 23 testa na mutantnim miševima, ali još uvijek nisu uočene značajne abnormalnosti.[21]
Interakcije
urediPokazalo se da S100B ima interakcije sa:
Reference
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Dopunska literatura
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Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.