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Imikhiqizo

I-Catalog peptide GsMTx4: I-Spider Venom Peptide Ivimbela Iziteshi Ezizwelayo

Incazelo emfushane:

I-GsMTx4 iyi-peptide eyinsalela engama-35 enesakhiwo sefindo le-cysteine, etholakala ebuhlungwini be-Grammostola rosea spider.Ibophezela futhi ivimbele iziteshi ze-cationic mechanosensitive (MSCs), okungamaprotheni e-membrane adlulisa ama-mechanical stimus abe yi-ion fluxes.Ama-MSC alawula izinqubo ezihlukahlukene ze-physiological and pathological, ezifana ne-hemodynamics, i-nociception, ukulungiswa kwezicubu, ukuvuvukala, i-tumorigenesis, kanye ne-stem cell fate.I-GsMTx4 ilungisa lezi zinqubo ngokuthinta imisebenzi yeselula eqondiswa yi-MSC, njengamandla olwelwesi, ukusayinda kwe-calcium, ukufinyela, nokubonakaliswa kofuzo.I-GsMTx4 isetshenziswe kumamodeli ezilwane namaseli ukuhlola amandla ayo okwelapha ku-neuroprotection, anti-inflammation, anti-cancer, kanye nobunjiniyela bezicubu.I-GsMTx4 iyithuluzi elibalulekile lesayensi yezemithi lokucacisa indima yama-MSC kuPhysiology kanye ne-pathology.


Imininingwane Yomkhiqizo

Omaka bomkhiqizo

Mayelana Nale Nto

I-GsMTx4 iyi-peptide engu-35-amino acid enamabhondi amane e-disulfide akha i-cysteine ​​knot motif, okuyisici esivamile sesakhiwo sama-peptide amaningi e-spider venom enikeza ukuzinza nokucacisa.Indlela yokusebenza ye-GsMTx4 ayicaciswanga ngokugcwele, kodwa kukholakala ukuthi ibophezela ezizindeni ezingaphandle kwamaselula noma i-transmembrane ye-cationic MSCs futhi ivimbe ukuvuleka kwembobo noma ukuvuleka kwawo ngokushintsha ukuhlangana kwawo noma ukungezwani kwe-membrane.I-GsMTx4 iboniswe ukuthi ivimbela ama-MSC amaningana e-cationic ngokukhetha okuhlukile namandla.Isibonelo, i-GsMTx4 ivimbela i-TRPC1 nge-IC50 ka-0.5 μM, i-TRPC6 ene-IC50 ka-0.2 μM, i-Piezo1 ene-IC50 ka-0.8 μM, i-Piezo2 ene-IC50 ka-0.3 μM, kodwa ayinawo umthelela ku-TRP40 ku-TRP41 μM.(Bae C et al 2011, Biochemistry)

I-Dispaly yomkhiqizo

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Kungani Khetha Thina

I-GsMTx4 isetshenziswe njengethuluzi lekhemisi lokufunda umsebenzi nokulawulwa kwama-cationic MSCs ezinhlotsheni zamaseli nezicubu ezihlukene.Ezinye zezibonelo yilezi:
I-GsMTx4 ingavimba ama-MSC acushwa ngokunwebeka kuma-astrocyte, amaseli enhliziyo, amaseli emisipha abushelelezi namaseli emisipha yamathambo.Ama-astrocyte amangqamuzana amise okwenkanyezi asekela ubuchopho nomgogodla.Amaseli enhliziyo amangqamuzana akha imisipha yenhliziyo.Amaseli emisipha ebushelelezi amaseli alawula ukunyakaza kwezitho ezifana nesisu nemithambo yegazi.Amaseli emisipha yohlaka amangqamuzana avumela ukunyakaza komzimba ngokuzithandela.Ngokuvimbela ama-MSC kulawa maseli, i-GsMTx4 ingashintsha izakhiwo zawo zikagesi, amazinga e-calcium, ukufinyela nokukhululeka, kanye nokubonakaliswa kofuzo.Lezi zinguquko zingathinta indlela la maseli asebenza ngayo ngokujwayelekile noma ezimeni zezifo (Suchyna et al., Nature 2004; Bae et al., Biochemistry 2011; Ranade et al., Neuron 2015; Xiao et al., Nature Chemical Biology 2011)

I-GsMTx4 ingaphinde ivimbe uhlobo olukhethekile lwe-MSC olubizwa nge-TACAN, oluhilelekile ekuphenduleni ubuhlungu.I-TACAN iwumzila ovezwa kumaseli ezinzwa ezwa ubuhlungu.I-TACAN yenziwa isebenze ngokushukumisa kwemishini, njengokucindezelwa noma ukuncinza, futhi idala ukuzwa izinhlungu.I-GsMTx4 inganciphisa umsebenzi we-TACAN futhi yehlise ukuziphatha kobuhlungu kumamodeli ezilwane zobuhlungu bemishini (Wetzel et al., Nature Neuroscience 2007; Eijkelkamp et al., Nature Communications 2013)

I-GsMTx4 ingavikela ama-astrocyte kubuthi obubangelwa i-molecule ebizwa ngokuthi i-lysophosphatidylcholine (LPC), engumxhumanisi we-lipid obangela ukulimala kwengqondo nomgogodla.I-LPC ingakwazi ukusebenzisa ama-MSC kuma-astrocyte futhi iwabangele ukuthi athathe i-calcium eningi, okuholela ekucindezelekeni kwe-oxidative nokufa kweseli.I-GsMTx4 ingavimbela i-LPC ekusebenziseni ama-MSC kuma-astrocyte futhi iwavikele ebusheni.I-GsMTx4 futhi inganciphisa ukulimala kobuchopho futhi ithuthukise ukusebenza kwezinzwa kumagundane ajovwe nge-LPC (Gottlieb et al., Ijenali ye-Biological Chemistry 2008; Zhang et al., Ijenali ye-Neurochemistry 2019)

I-GsMTx4 ingalungisa ukuhlukaniswa kwe-neural stem cell ngokuvimbela uhlobo oluthile lwe-MSC olubizwa nge-Piezo1, oluvezwa kumaseli e-neural stem.Amaseli e-Neural stem angamaseli angenza ama-neurons amasha noma ezinye izinhlobo zamaseli obuchopho.I-Piezo1 iyisiteshi esenziwa kusebenze izinkomba zemishini ezivela endaweni ezungezile, njengokuqina noma ingcindezi, futhi ithonya indlela amangqamuzana e-neural stem anquma ngayo ukuthi yiluphi uhlobo lweseli okufanele lube.I-GsMTx4 ingaphazamisa umsebenzi we-Piezo1 futhi iguqule ukuhlukaniswa kwe-neural stem cell kusuka kuma-neurons kuya kuma-astrocyte (Pathak et al., Journal of Cell Science 2014; Lou et al., Cell Reports 2016)

Xhumana nathi

Singumkhiqizi we-polypeptide e-China, esineminyaka eminingana yokuhlangenwe nakho okuvuthiwe ekukhiqizeni i-polypeptide.I-Hangzhou Taijia Biotech Co., Ltd. ingumkhiqizi wezinto ezingavuthiwe ze-polypeptide, enganikeza amashumi ezinkulungwane zezinto zokusetshenziswa ze-polypeptide futhi ingenziwa ngokwezifiso ngokwezidingo.Izinga lemikhiqizo ye-polypeptide lihle kakhulu, futhi ubumsulwa bungafinyelela ku-98%, okuye kwaqashelwa abasebenzisi emhlabeni wonke.Siyakwamukela ukuthi uxhumane nathi.


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