UTICAJ 2,4-DIAMINOBUTERNE KISELINE NA PROTEINE KOJI UČESTVUJU U RAZVIĆU  MORFOMETRIJSKI MERLJIVIH PARAMETARA OKA KOD ZEBRICE: IN SILICO ANALIZA

Milica Milošević; Nikola Mitović; Maša Ristić; Ljubica Dimitrijević; Sanjin Kovačević; Jelena Nešović-Ostojić; Marija Stanojević; Svetolik Spasić

doi:10.5937/zdravzast53-52916

Milica Milošević Institut za kardiovaskularne bolesti „Dedinje”, Beograd, Republika Srbija
Nikola Mitović Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija
Maša Ristić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski klinički centar Srbije, Beograd, Republika Srbija
Ljubica Dimitrijević Specijalna Bolnica „Sveti Sava”, Beograd, Republika Srbija
Sanjin Kovačević Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija
Jelena Nešović-Ostojić Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija
Marija Stanojević Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija
Svetolik Spasić Institut za patološku fiziologiju, Medicinski fakultet Univerzitet u Beogradu, Beograd, Republika Srbija

DOI: https://doi.org/10.5937/zdravzast53-52916

Ključne reči: bioinformatika, razviće oka, 2,4-DABA, zebrice

Sažetak

Uvod/cilj: 2,4- diaminobuterna kiselina (2,4-DABA), ekscitatorna amino-kiselina sa dokazanim neurotoksičnim efektom se nalazi u vodenim ekosistemima, sa potencijalom za akumulaciju u biljnim i u životinjskim organizmima. S obzirom da je dokazan njen neurotoksični, hepatotoksični i potencijalno kancerogeni efekat postavlja se pitanje moguće embriotoksičnosti. Zahvaljujući velikoj homologiji sa ljudskim genomom, dinamika i morfologija razvića se može proučavati na zebricama (lat. Danio rerio), koje predstavljaju dobar model sistem za ispitivanje razvića i razvojnih abnormalnosti. Cilj je ispitivanje uticaja 2,4-DABA-e na proteine ključne u razviću oka zebrica pomoću molekularnog dokinga.

Metode: Inicijalno je urađen skrining celokupnog genoma korišćenjem FINDSITEcomb softvera, preciznom analizom je selektovano 1119 proteina iz baze kojima smo utvrđivali stepen homologije, tkivno specifičnu ekspresiju i vreme ekspresije. Šest proteina koji su ispunili tražene kriterijume, analizirani su u AutoDock Vina programu molekularnim dokingom.

Rezultati: Interakcija fzd8a proteina i 2,4-DABA-e ispoljila je najnižu vrednost Gibsove slobodne energije od - 4,6 kCal/mol, dok je najviša od - 3,4 kCal/mol zabeležena u interakciji sa proteinom pbx4. Takođe, uočena je sličnost aminokiselinske sekvence u proteinima za koje se vezivala 2,4-DABA, koja se ogledala u aminokiselinama koje u svom sastavu imaju –SH grupu.

Zaključak: Sprovedenim istraživanjem pokazano je da 2,4-DABA može ostvarivati svoje efekte na razvoj oka, tokom celog perioda. Rezultate in silico analiza ne treba posmatrati izolovano, već kao početni korak i smernice za istraživanja u in vivo uslovima. Stoga naša studija treba biti dopunjena rezultatima ispitivanja na živim embrionima.

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