Toksičnost bilirubina za astrocite možganske skorje podgane

Vrabič, Ajda (avtor), Lipnik Štangelj, Metoda (mentor)

Bilirubin je endogena snov, ki nastaja pri razgradnji hemoglobina. Kadar ga je v organizmu preveč, deluje toksično. Znana je toksičnost bilirubina v osrednjem živčevju, kjer se odlaga v bazalnih ganglijih, hipokampusu in možganskem deblu, vključno s ponsom in srednjimi možgani. Bilirubin je tudi močan antioksidant, ki osrednje živčevje varuje pred oksidativnim stresom, ki ga med drugim povzroča tudi stavrosporin. Cilj naše naloge je bil ugotoviti vpliv bilirubina na apoptozo in nekroptozo kot dve obliki regulirane celične smrti astrocitov. Zanimalo nas je tudi, kako bilirubin vpliva na tvorbo ATP, ki služi kot indikator fiziološkega stanja celic. Kot eksperimentalni model smo uporabili kulture astrocitov možganske skorje novorojenih podgan. Z analizo celic na pretočnem citometru smo ugotovili, da bilirubin nima vpliva na apoptozo astrocitov, medtem ko v visokih koncentracijah (100 nM in 250 nM) poveča delež nekroptotičnih celic. Po drugi strani je v primeru nekroptoze bilirubin izkazal hormetičen učinek, kjer je v nizki koncentraciji (10 nM) deloval zaščitno in je zmanjšal nekroptozo astrocitov, sproženo z 1 µM stavrosporinom. Vpliva bilirubina na količino ATP v astrocitih v uporabljenih eksperimentalnih razmerah nismo dokazali. Zaključili smo, da je bilirubin v visokih koncentracijah toksičen za astrocite, medtem ko v nizkih koncentracijah lahko deluje tudi zaščitno.

• Jezik: Slovenski jezik
• Ključne besede: bilirubin, astrociti, regulirana celična smrt, apoptoza, nekroptoza, hormeza
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: BF - Biotehniška fakulteta
• Leto izida: 2021
• PID: 20.500.12556/RUL-131107
• Datum objave v RUL: 23.09.2021

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Toxicity of bilirubin to rat cortical astrocytes

Izvleček

Bilirubin is an endogenous substance, formed during the breakdown of hemoglobin. When there is too much of it in the body it becomes toxic. Bilirubin toxicity is well known in the central nervous system, where it is deposited in the basal ganglia, hippocampus and brainstem, including the pons and midbrain. Bilirubin is also a powerful antioxidant, which protects the central nervous system from oxidative stress, caused by staurosporine. The aim of our study was to determine the effect of bilirubin on apoptosis and necroptosis as two forms regulated cell death of astrocytes. We were also interested in how bilirubin affects the production of ATP, which serves as an indicator of cell's physiological state. As an experimental model we used astrocyte cultures of the cerebral cortex of newborn rats. As a result of a flow cytometer analysis bilirubin was found to have no effect on astrocyte apoptosis, whereas at high concentrations (100 nM and 250 nM) it increased the proportion of necroptotic cells. On the other hand, in the case of necroptosis, bilirubin has shown a hormestic effect, where at a low concentration (10 nM) it acted protectively and reduced astrocyte necroptosis, triggered by 1 µM staurosporine. Our experimental conditions did not show any effect of bilirubin on the amount of ATP in astrocytes. We came to the conclusion, that bilirubin in high concentrations is toxic to astrocytes, while in low concentrations it can also act protectively.

• Ključne besede: bilirubin, astrocytes, regulated cell death, apoptosis, necroptosis, hormesis