Polimorfizam gena, ekspresija i enzimska aktivnost monoamin oksidaze A u ljudskoj posteljici

master's thesis

• Title (english): Gene polymorphism, expression and enzyme activity of monoamine oxidase A in human placenta
• Author: Kristina Nikolić
• Mentor: Jasminka Štefulj (mentor)
• Mentor: Dubravka Hranilović (komentor)
• Committee member: Dubravka Hranilović (predsjednik povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Anamaria Štambuk (član povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-02-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Posteljica je privremeni fetalni organ od presudne važnosti za normalan tijek trudnoće. Serotonin, hormon i neurotransmiter, sudjeluje u regulaciji razvoja i različitih funkcija posteljice. Ključni katabolički enzim serotonina je monoamin oksidaza (MAO), flavoenzim čija izoforma MAOA je bogato zastupljena u posteljici. Cilj ovog rada bio je doprinijeti boljem razumijevanju svojstava i regulacije MAOA u ljudskoj posteljici. U tu svrhu, skupini novorođenčadi (n=143) je genotipiziran polimorfizam MAOA-uVNTR, potencijalni kandidat za regulaciju transkripcijske aktivnosti gena MAOA. U uzorcima posteljice određene su razine mRNA MAOA metodom kvantitativne lančane reakcije polimerazom u stvarnom vremenu (RT-qPCR) te kinetički parametri (Vmax, KM) MAOA spektrofluorimetrijskom metodom uz uporabu kinuramina kao supstrata. Razine mRNA MAOA u posteljici se nisu razlikovale u ovisnosti o genotipu MAOA-uVNTR, sugerirajući da ovaj polimorfizam ne igra bitnu ulogu u regulaciji ekspresije gena MAOA u humanoj posteljici. Razina mRNA MAOA i kinetički parametri MAOA nisu se razlikovale između muške i ženske novorođenčadi. Uočena je pozitivna korelacija između razine mRNA MAOA i enzimske aktivnosti MAOA. Dobiveni rezultati pružaju temelj za daljnja istraživanja mehanizama regulacije gena MAOA u ljudskoj posteljici i potencijalne uloge ovog enzima u različitim komplikacijama trudnoće povezanim s nepravilnom funkcijom posteljice.

Abstract (english)

The placenta is a temporary fetal organ that is crucial for normal course of pregnancy. Serotonin, a hormone and a neurotransmitter, is involved in regulating the development and various functions of the placenta. A key catabolic enzyme of serotonin is monoamine oxidase (MAO), a flavoenzyme whose isoform MAOA is abundant in the placenta. The aim of this thesis was to contribute to a better understanding of the properties and regulation of MAOA in human placenta. For this purpose, a group of newborns (n=143) were genotyped for MAOA-uVNTR polymorphism, a potential candidate for regulation of transcriptional activity of MAOA gene. In placenta samples MAOA mRNA levels were determined using the reverse transcription-quantitative real-time PCR (RT-qPCR) method and the kinetic parameters (Vmax, KM) of MAOA were determined by the spectrofluorimetric method using kynuramine as a substrate. Placental MAOA mRNA levels did not differ depending on the MAOA-uVNTR genotype, suggesting that this polymorphism does not play major role in the regulation of MAOA gene expression in the human placenta. MAOA mRNA level and MAOA kinetic parameters did not differ between male and female newborns. A positive correlation was observed between MAOA mRNA levels and MAOA enzyme activity. The obtained results provide a basis for further research into the mechanisms of MAOA gene regulation in the human placenta and the potential role of this enzyme in various pregnancy complications associated with impaired placental function.

• Keywords: MAOA; placenta; 5-hidroksitriptamin; genska varijabilnost; enzimska aktivnost
• Keywords (english): MAOA; placenta; 5-hydroxytryptamine; genetic variability; enzymatic activity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:876433
• Project: Number: IP-2018-01-6547; Title: Utjecaj majčinog metaboličkog stanja na serotoninski sustav posteljice i neonatusa: od metilacije DNA do funkcije proteina; Acronym: PLANS; Leader: Jasminka Štefulj; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Molecular Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra molekularne biologije (sveučilišni/a magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-03-13 11:34:33