Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması

Abstract

Karaciğer rejenerasyonu çok sayıda kompleksin görev aldığı karmaşık bir mekanizmadır. Rejenerasyon, karaciğerin %70’nin çıkarılmasıyla tetiklenir ve hücreler, 1-2 bölünmeden sonra tekrar G0 fazına geçer. Karaciğer rejenerasyonu sırasında mitokondrilerin şekilsel olarak bozulduğu, krista sayının arttığı, şiştiği ancak; ilerleyen saatlerde normale döndüğü bilinmektedir. Karaciğer rejenerasyonu sırasında mitokondrilerin nasıl normale döndüğü ile ilgili moleküler mekanizmalar açık değildir. Mitokondrilerin, günümüzde, enerji üretimi dışında farklı mekanizmalarla (mitofaji, mitokondriyal fizyon, kalsiyum homeostazisi Fe-S protein sentezi gibi) ilişkisi açıktır. Bu nedenle çalışmamızda parsiyal hepatektomi ile tetiklenen karaciğer rejenerasyonunda Drp1 gen ekspresyonu ve DRP1, MUL1 protein miktarları belirlenerek MUL1 aracılı mitofaji/mitokondriyal fizyon mekanizmasının olası aktivasyonu rejenerasyonun 6, 12, 24 saatlerine göre değerlendirilmiştir. Elde edilen veriler sonucunda; MUL1 protein miktarlarında; PH rejenerasyon gruplarında, Sham gruplarına göre düşüş olduğu belirlenmiştir. Drp1 değerlendirildiğinde genel olarak PH gruplarında düşmesine rağmen PH12. saatte meydana gelen hafif artış ilginçtir. Drp1 ekspresyonu ve protein miktarındaki bu artışın mitofajiden ziyade farklı mekanizmalarla (Kalsiyum homeostazı, ERAD) ilişkili olabileceğini düşündürüyor. Bunun için daha fazla araştırmaya ihtiyaç vardır.

Keywords

• Mitofaji
• Mitokondriyal Fizyon
• ERAD
• Drp1
• Mul1
• Karaciğer Rejenerasyonu
• Sıçan

Investigation of Possible Mitochondrial Fission Mechanism in Liver Regeneration Triggered by Partial Hepatectomy

Abstract

Liver regeneration is a complex mechanism in which a large number of complexes are involved. Regeneration is triggered by the removal of 70% of the liver, and the cells go back into the G0 phase after 1-2 divisions. It is known that during liver regeneration, mitochondria are deformed, swollen, increased crista. In the later hours of regeneration, it is observed that mitochondria return to normal. The molecular mechanisms involved in how mitochondria return to normal during liver regeneration are not clear. Mitochondria do not only produce energy; It is also associated with the mechanisms of mitophagy, mitochondrial fission, calcium homeostasis, Fe-S protein synthesis. In our study, Drp1 gene expression and DRP1, MUL1 protein amounts were determined according to 6, 12, 24 hours of regeneration As a result of the data obtained; MUL1 protein amounts were decreased in the PH groups compared to the sham groups. Although Drp1 expression and DRP1 protein quantities generally fall in PH groups, the slight increase in PH12 is interesting. We think that Drp1 expression and an increase in protein amount may be related to different mechanisms from mitophagy (Calcium homeostasis, ERAD). We think that Drp1 expression and protein quantity increases may be related to different mechanisms (Calcium homeostasis, ERAD) than mitophagy. More researches are needed.

Keywords

• Mitophagy
• Mitochondrial Fission
• ERAD
• Drp1
• Mul1
• Liver Regeneration
• Rat

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