INTERAKCIJE PROKAINA SA KLJUČNIM PROTEINIMA U RAZVIĆU SRCA ZEBRICA:  IN SILICO ANALIZA

Nikola Mitović; Milica Milošević; Maša Ristić; Ljubica Dimitrijević; Sanjin Kovačević; Jelena Nešović Ostojić; Marija  Stanković

doi:10.5937/zdravzast53-52914

Nikola Mitović Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija https://orcid.org/0000-0002-4642-0110
Milica Milošević Institut za kardiovaskularne bolesti „Dedinje”, Beograd, Republika Srbija https://orcid.org/0009-0004-6138-8819
Maša Ristić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski klinički centar Srbije, Beograd, Republika Srbija https://orcid.org/0009-0003-9425-203X
Ljubica Dimitrijević Specijalna Bolnica „Sveti Sava”, Beograd, Republika Srbija https://orcid.org/0009-0000-5861-3422
Sanjin Kovačević Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija https://orcid.org/0000-0001-5905-7173
Jelena Nešović Ostojić Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija https://orcid.org/0000-0002-0172-5789
Marija Stanković Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija https://orcid.org/0000-0001-5187-6430

DOI: https://doi.org/10.5937/zdravzast53-52914

Ključne reči: prokain, razvoj srca, zebrice, molekularni doking

Sažetak

Uvod/Cilj: Prokain je lokalni anestetik iz aminoestarske grupe koji blokira natrijumove voltažno-zavisne kanale. S obzirom na to da može proći kroz placentu u jonizovanom obliku, postavlja se pitanje njegovog uticaja na embrionalni razvoj. Zebrice, koje imaju značajan stepen homologije sa ljudskim genomom, omogućavaju proučavanje razvoja kardiovaskularnog sistema sa pouzdanom ekstrapolacijom na čoveka. Ispitivanje uticaja prokaina na ključne proteine u razvoju srca zebrica pomoću molekularnog dokinga.

Metode: Prvo je izvršen skrining interakcije prokaina i celog ljudskog proteoma koristeći FINDSITEcomb softver. Na osnovu značajnih interakcija sa visokim stepenom preciznosti analize, selektovano je 113 proteina. Pomoću ZFIN baze je određen stepen homologije između selektovanih ljudskih proteina sa zebričinim, tkivna-specifičnost i vremena ekspresije. Devet proteina su ispunili sve kriterijume: kcnh6a, kcnh7, kcnh5a, kcnh2a, psen2, rbfa i zfpl1 i dalje su ispitivani molekularnim dokingom u AutoDock Vina programu.

Rezultati: Većina proteina se eksprimira visokom stopom tokom blastule. Doking rezultati su pokazali da scn1laa protein i prokain imaju najnižu vrednost Gibsove slobodne energije (-6 kCal/mol), dok je za zfp11 protein vrednost bila najviša (-4,4 kCal/mol). Vezivanje prokaina na ispitivane proteine pokazalo je slične aminokiselinske sekvence unutar iste familije proteina.

Zaključak: Prokain ostvaruje interakcije sa proteinima uključenim u razvoj srca zebrica u in silico uslovima. Dalje analize na živim embrionima su potrebne kako bi se dopunili ovi rezultati.

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