Beïnvloeden metalen de werking van jouw DNA?
Metalen zijn onmisbaar voor ons lichaam—ze spelen een sleutelrol in onze groei, ontwikkeling en algehele gezondheid. Maar wat als deze essentiële moleculen ook invloed hebben op de meest fundamentele blauwdruk van ons bestaan: ons DNA? In dit onderzoek trachten we een antwoord te vinden op de fascinerende vraag of ijzer kan binden aan histonen, de eiwitten die onze genen aan- en uitzetten. Hoe beïnvloedt dit onze genen en hoe we zijn?
Een bibliotheek vol genen
Ons DNA kan voorgesteld worden als een grote bibliotheek vol boeken, waarin elk boek een gen vertegenwoordigt. Deze boeken geven de instructies voor het maken van eiwitten, de bouwstenen van ons lichaam. Deze eiwitten bepalen veel van onze eigenschappen, zoals je huidskleur, de kleur van je ogen en de werking van je lichaam. Ons DNA draagt als het ware het ontwerp voor je bestaan. Toch kunnen twee personen met exact hetzelfde DNA er heel verschillend uitzien of zich anders gedragen. Neem bijvoorbeeld eeneiige tweelingen: waarom kan één helft van een eeneiige tweeling ten prooi vallen aan een hartaandoening op jongere leeftijd, terwijl de andere zus kerngezond blijft? Dit fenomeen is te danken aan epigenetica, waarbij de invloed van omgevingsfactoren en levensstijl ervoor zullen zorgen dat bepaalde genen of boeken meer worden ‘uitgelezen’ dan andere. Hierdoor kunnen mensen met dezelfde genetische aanleg heel verschillende levens leiden.
Histonen als sloten
Niet alle genen hoeven continu actief te zijn. Ze worden alleen gebruikt als dat nodig is. Om deze beschikbaarheid te reguleren, kan het DNA worden opgerold rond histonen (een bepaald type eiwit) om de genetische informatie compact op te vouwen. Wanneer DNA zich oprolt rond een complex van acht histonen, noemen we dat ook wel een nucleosoom. In opgevouwen toestand is het DNA niet beschikbaar en kunnen er geen eiwitten worden aangemaakt - die genen staan dan als het ware ‘uit’. Je kunt histonen zien als de sloten op de boeken in onze genetische bibliotheek: wanneer ze op slot zijn, is de informatie binnenin ontoegankelijk. Welke genen 'open' of 'op slot' zijn, bepaalt voor een groot deel hoe we eruitzien en functioneren.
Metalen zijn van levensbelang
Naast DNA en eiwitten spelen metalen ook een belangrijke rol in het lichaam. We kunnen niet leven zonder metalen. Bekende mineralen zoals calcium en fosfor zorgen bijvoorbeeld voor sterke botten, natrium, kalium en chloride daarentegen helpen bij het reguleren van onze vochtbalans. Bovendien bevat ongeveer de helft van alle gekende eiwitten een metaal, wat essentieel is voor de werking van dat eiwit. Een goed voorbeeld hiervan is hemoglobine, een belangrijk eiwit in ons bloed dat dankzij ijzer zuurstof van de longen naar de rest van het lichaam transporteert.
Aan de andere kant hebben metalen ook een keerzijde. Ze kunnen oxidatieve stress veroorzaken, wat betekent dat ze ervoor zorgen dat zuurstof in een schadelijke vorm in de cellen komt. Dit kan ons DNA beschadigen, wat op zijn beurt kan leiden tot kanker. Daarom hebben veel onderzoeken gekeken naar hoe metalen bijdragen aan DNA-schade. De rol van deze metalen op onze ‘sloten’ is echter nog niet helemaal duidelijk.
Kunnen metalen onze genen reguleren?
Omdat metalen zo belangrijk zijn, rijst de vraag: spelen ze ook een rol in het reguleren van onze genen? Epigenetica is een complex proces waar veel factoren op elkaar inspelen en elkaar beïnvloeden. Naast histonen, die functioneren als 'sloten' op onze genen, kunnen andere moleculen en stoffen de genen verder vergrendelen of juist toegankelijk maken. Eén van deze factoren zijn acetylaties, die de sloten 'verzwakken' waardoor het DNA zich ontrolt en weer gelezen kan worden. Maar wat als metalen deze sloten ook kunnen beïnvloeden? Recente studies hebben aangetoond dat koper kan binden aan histonen. Aangezien ijzer in veel eiwitten een rol speelt, is de volgende vraag: kan ijzer ook aan histonen binden? En zou dit invloed hebben op welke genen actief zijn?
De zoektocht naar ijzerbinding aan histonen
Om te onderzoeken of ijzer zich daadwerkelijk aan histonen kan binden, moeten we eerst een 3D-model maken van het nucleosoom—het complex van DNA en 8 histonen. Om dit complex in grote hoeveelheden te produceren, maken we gebruik van verschillende stappen. Dit proces begint met genetisch gemodificeerde bacteriën, die de instructies krijgen om de benodigde eiwitten aan te maken. Vervolgens worden deze eiwitten gezuiverd uit de bacteriën en samengebracht om het complex te vormen. Dit proces is in realiteit niet evident. Het nucleosoom bestaat uit vier verschillende soorten histonen, wat betekent dat elke histon zijn eigen specifieke stappen nodig heeft om geoptimaliseerd te worden. Desondanks slaagden we erin om drie van de vier histonen aan te maken. Het onderzoek naar het vierde histon is nog in volle gang, maar binnenkort kunnen we wellicht vaststellen of ijzer in staat is om aan histonen te binden en zo onze genen te beïnvloeden.
Het begrijpen van hoe metalen zoals ijzer invloed kunnen hebben op onze genen opent nieuwe mogelijkheden in de geneeskunde. Als blijkt dat ijzer en andere metalen een rol spelen in het 'aanzetten' of 'uitzetten' van genen, zou dit kunnen leiden tot baanbrekende behandelingen voor genetische aandoeningen of ziekten zoals kanker. Bepaalde therapieën zouden juist de aanwezigheid van de metalen kunnen gebruiken om kankercellen onschadelijk te maken of hun ontwikkeling af te remmen.
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