Zogulitsa

Kudzikundikira kwa nyukiliya ya mtundu wosinthika wa protein ya nyukiliya Lamin-A, yotchedwa Progerin (PG) kapena Lamin AΔ50, imapezeka ku Hutchinson-Gilford Progeria Syndrome (HGPS) kapena Progeria, matenda okalamba omwe amafulumira.Chimodzi mwazizindikiro zazikulu za vuto la chibadwa ichi ndikutaya kwamafuta am'munsi chifukwa cha lipodystrophy.Tidapanga mokhazikika mawu amunthu PG ndi GFP -Green Fluorescent Protein- monga ulamuliro m'maselo a 3T3L1 pogwiritsa ntchito lentiviral system kuphunzira Zotsatira za kufotokoza kwa PG mu mphamvu yosiyanitsira ya mzere wa cell iyi, imodzi mwamitundu yogwiritsidwa ntchito kwambiri ya adipogenic.Quantitative proteomics (iTRAQ) idachitidwa kuti iphunzire momwe PG ikuchulukira.Mapuloteni angapo osinthidwa adatsimikiziridwa ndi immunoblotting ndi PCR yeniyeni.Ntchito ya mitochondrial idawunikidwa ndi kuyeza kwa a) ntchito ya mitochondrial basal, b) kupanga superoxide anion ndi c) kuthekera kwapayekha kwa zovuta zosiyanasiyana zaunyolo wopumira. kuchepa kwa kuchuluka kwa kuchuluka komanso kuwonongeka kwa mphamvu ya adipogenic poyerekeza ndi kuwongolera.Kuwunika kwa kuchuluka kwa proteinomics kunawonetsa mapuloteni 181 kwambiri (p <0.05) osinthidwa mu PG-expressing preadipocytes.Ntchito ya Mitochondrial imawonongeka m'maselo a PG-expressing.Mwachindunji, tazindikira kuwonjezeka kwa ntchito ya zovuta I ndi kuchulukitsa kwa superoxide anion.Kukulitsa ndi Reactive Oxygen Species (ROS) kumapangitsa kuti pakhale kuchepa kwa autophagic proteolysis monga zavumbulutsidwa ndi LC3-II/LC3-I ratio.PG mawu m'maselo a 3T3L1 amalimbikitsa kusintha kwa Biological process zingapo, kuphatikiza kapangidwe ka cytoskeleton, lipid metabolism, calcium. kuwongolera, kumasulira, kupindika kwa mapuloteni ndi kupanga mphamvu ndi mitochondria.Deta yathu imalimbitsa chopereka cha ROS kudzikundikira ku phenotype yokalamba msanga ndikukhazikitsa mgwirizano pakati pa kusagwira ntchito kwa mitochondrial ndi kutayika kwa proteostasis mu HGPS.