Uloga biomarkera redoks homeostaze u nastanku i progresiji svetloćelijskog karcinoma bubrežnog parenhima
Sažetak
Svetloćelijski karcinom bubrežnog parenhima (sKBP) predstavlja najčešći i najagresivniji podtip karcinoma bubrežnog parenhima koji se u najvećem broju slučajeva otkrije u već uznapredovaloj formi. Smatra se da bi ga trebalo posmatrati kao metaboličko oboljenje s obzirom da su za njegov nastanak ključne promene u metaboličkim putevima, kao i poremećaj redoks homeostaze. Kako su određene promene karakteristične za nastanak tumora a druge za metastatski proces, prepoznavanje metaboličkih modifikacija moglo bi da ukaže na stadijum tumorske progresije. Hipoksijom indukovani faktor, kao jedan od faktora koji kontroliše transkripciju gena koji kodiraju enzime uključene u proces glikolize, kao i faktor koji utiče na akumulaciju lipida, ima značajnu ulogu u nastanku sKBP. Pored toga, poremećena redoks homeostaza indukuje Keap1/Nrf2 signalni put, koji dalje utiče na sintezu enzima uključenih u drugu fazu detoksikacije, uključujući glutation transferaze. Njihovo pojačano prisustvo, naročito Pi klasa, može inhibirati proces programirane smrti ćelija što je esencijalno za progresiju tumora. I vodonik peroksid (H2O2) ima ulogu u prenosu signala u redoks-senzitivnim putevima S obzirom da su superoksid dizmutaza i glutation peroksidaza dva enzima uključena u stvaranje i razgradnju H2O2, aktivnost ovih enzima značajno utiče na nivo ovog molekula i, posledično, na sposobnost ćelija sKBP da izbegnu negativan efekat reaktivnih kiseoničnih radikala.
Reference
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