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Ikhathalogu yepeptide GsMTx4: I-Peptide Yesigcawu Esinobuhlungu bunqanda iMechanosensitive Channels Umfanekiso obonisiweyo
  • Ikhathalogu yepeptide GsMTx4: I-Peptide Yesigcawu iNqanda iMechanosensitive Channels

Ikhathalogu yepeptide GsMTx4: I-Peptide Yesigcawu iNqanda iMechanosensitive Channels

Inkcazelo emfutshane:

I-GsMTx4 yi-35-residue peptide ene-cysteine ​​knot structure, ephuma kwityhefu ye-Grammostola rosea spider.Ibophelela kwaye inqanda iziteshi ze-cationic mechanosensitive (MSCs), eziyiprotheni ze-membrane eziguqula i-mechanical stimuli kwi-ion fluxes.Ii-MSCs zilawula iinkqubo ezahlukeneyo ze-physiological and pathological, ezifana ne-hemodynamics, i-nociception, ukulungiswa kwezicubu, ukuvuvukala, i-tumorigenesis, kunye ne-stem cell fate.I-GsMTx4 imodareyitha ezi nkqubo ngokuchaphazela imisebenzi yeselula ye-MSC-mediated, njenge-membrane enokubakho, ukubonakalisa i-calcium, i-contractility, kunye ne-gene expression.I-GsMTx4 isetyenziswe kwiimodeli zezilwanyana kunye neeseli ukuhlola amandla ayo onyango kwi-neuroprotection, anti-inflammation, anti-cancer, kunye nobunjineli bezicubu.I-GsMTx4 sisixhobo esixabisekileyo sokuxuba amayeza sokucacisa indima yee-MSC kwifiziyoloji nakwi-pathology.


Iinkcukacha zeMveliso

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Malunga nale Nto

I-GsMTx4 yi-35-amino acid peptide eneebhondi ezine ze-disulfide ezenza i-cysteine ​​knot motif, neluphawu oluqhelekileyo lolwakhiwo lweepeptides ezininzi ze-spider venom ezinikezela uzinzo kunye neenkcukacha.Indlela yokusebenza ye-GsMTx4 ayicaciswanga ngokupheleleyo, kodwa kukholelwa ukuba ibophelela kwi-extracellular okanye i-transmembrane domains ye-cationic MSCs kwaye ivalela ukuvuleka kwepore okanye i-gating yabo ngokuguqula ukuhambelana kwabo okanye ukunyanzeliswa kwe-membrane.I-GsMTx4 ibonakaliswe ukuba inqanda ii-MSC ezininzi ze-cationic ngokukhetha okwahlukileyo kunye namandla.Umzekelo, i-GsMTx4 inqanda i-TRPC1 nge-IC50 ye-0.5 μM, i-TRPC6 ene-IC50 ye-0.2 μM, i-Piezo1 ene-IC50 ye-0.8 μM, i-Piezo2 ene-IC50 ye-0.3 μM, kodwa ayinayo impembelelo kwi-TRP40 ukuya kwi-TRP41 μM.(Bae C et al 2011, Biochemistry)

Imveliso Dispaly

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Kutheni Khetha Thina

I-GsMTx4 isetyenziswe njengesixhobo se-pharmacological ukufunda umsebenzi kunye nokulawulwa kwee-cationic MSCs kwiintlobo zeeseli ezahlukeneyo kunye nezicubu.Eminye yemizekelo yile:
I-GsMTx4 inokuthintela ii-MSCs ezenziwe zisebenze ngokuzolula kwii-astrocytes, iiseli zentliziyo, iiseli ze-muscle ezigudileyo kunye neeseli ze-skeletal muscle.I-astrocyte ziiseli ezimise okwenkwenkwezi ezixhasa ingqondo kunye nentambo yomgogodla.Iiseli zentliziyo ziiseli ezenza isihlunu sentliziyo.Iiseli zezihlunu ezigudileyo ziiseli ezilawula ukuhamba kwamalungu afana nesisu kunye nemithambo yegazi.Iiseli zezihlunu zeskeletal ziiseli ezenza intshukumo yomzimba ngokuzithandela.Ngokuvala ii-MSCs kwezi seli, i-GsMTx4 inokutshintsha iimpawu zabo zombane, amanqanaba e-calcium, ukufinyela kunye nokuphumla, kunye nokubonakaliswa kofuzo.Olu tshintsho lunokuchaphazela indlela ezi seli zisebenza ngayo ngokuqhelekileyo okanye kwiimeko zesifo (Suchyna et al., Nature 2004; Bae et al., Biochemistry 2011; Ranade et al., Neuron 2015; Xiao et al., Nature Chemical Biology 2011)

I-GsMTx4 inokuthintela uhlobo olukhethekileyo lwe-MSC ebizwa ngokuba yi-TACAN, ebandakanyekayo kwimpendulo yeentlungu.I-TACAN lijelo elibonakaliswa kwiiseli zemithambo-luvo eziva intlungu.I-TACAN ivulwe yi-stimuli ye-mechanical, efana noxinzelelo okanye i-pinching, kwaye ibangela ukuva kweentlungu.I-GsMTx4 inokunciphisa umsebenzi we-TACAN kunye nokunciphisa ukuziphatha kweentlungu kwiimodeli zezilwanyana zentlungu yomatshini (Wetzel et al., Nature Neuroscience 2007; Eijkelkamp et al., Unxibelelwano lweNdalo 2013)

I-GsMTx4 inokukhusela i-astrocytes kwi-toxicity eyenziwa yi-molecule ebizwa ngokuba yi-lysophosphatidylcholine (LPC), engumlamli we-lipid obangela umonakalo kwingqondo kunye nentambo yomgogodla.I-LPC inokusebenzisa ii-MSCs kwii-astrocytes kwaye ibangele ukuba bathathe i-calcium eninzi, ekhokelela kuxinzelelo lwe-oxidative kunye nokufa kweeseli.I-GsMTx4 inokuthintela i-LPC ekusebenziseni ii-MSCs kwii-astrocytes kwaye izikhusele kwityhefu.I-GsMTx4 inokunciphisa umonakalo wobuchopho kunye nokuphucula ukusebenza kwe-neurological kwiigundane ezifakwe i-LPC (Gottlieb et al., Ijenali ye-Biological Chemistry 2008; Zhang et al., Ijenali ye-Neurochemistry 2019)

I-GsMTx4 inokumodareyitha ulwahlulo lwe-neural stem cell ngokuthintela uhlobo oluthile lwe-MSC ebizwa ngokuba yi-Piezo1, ebonakaliswa kwiiseli ze-neural stem.Iiseli ze-Neural stem ziiseli ezinokwenza ii-neuron ezintsha okanye ezinye iintlobo zeeseli zengqondo.I-Piezo1 lijelo elenziwa lisebenze ngoomatshini bokusingqongileyo, njengokuqina okanye uxinzelelo, kwaye liphembelela indlela iiseli ze-neural stem ezithatha isigqibo sokuba luhlobo luni lweseli ekufuneka lube lulo.I-GsMTx4 inokuphazamisa umsebenzi we-Piezo1 kwaye itshintshe i-neural stem cell differentiation ukusuka kwi-neurons ukuya kwi-astrocytes (i-Pathak et al., I-Journal ye-Cell Science 2014; u-Lou et al., IiNgxelo zeSeli ze-2016)

Qhagamshelana nathi

Singumenzi wepolypeptide eTshayina, esineminyaka eliqela yamava aqolileyo kwimveliso yepolypeptide.I-Hangzhou Taijia Biotech Co., Ltd. yingcali yomenzi we-polypeptide ekrwada, enokubonelela amashumi amawaka ezinto ezikrwada ze-polypeptide kwaye inokwenziwa ngokweemfuno.Umgangatho weemveliso ze-polypeptide ugqwesileyo, kwaye ukucoceka kunokufikelela kwi-98%, eye yaqatshelwa ngabasebenzisi emhlabeni wonke.

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