Ibicuruzwa

Ikwirakwizwa rya kirimbuzi uburyo bwa mutant bwa poroteyine ya kirimbuzi Lamin-A, yitwa Progerin (PG) cyangwa Lamin AΔ50, iboneka muri Syndrome ya Hutchinson-Gilford Progeria (HGPS) cyangwa Progeria, indwara yihuta gusaza.Kimwe mu bimenyetso nyamukuru byiyi ndwara ni ugutakaza ibinure bya sub-cutane bitewe na lipodystrophy idasanzwe.Twashishikarije byimazeyo imvugo ya PG muntu na GFP -Icyatsi cya Fluorescent Protein- nkigenzura muri selile 3T3L1 dukoresheje sisitemu ya lentiviral kugirango twige ubushakashatsi Ingaruka ya imvugo ya PG mubushobozi bwo gutandukanya uyu murongo wimikorere, imwe muma moderi ikoreshwa cyane.Proteomics Quantitative (iTRAQ) yakozwe kugirango yige ingaruka zo kwirundanya kwa PG.Poroteyine nyinshi zahinduwe zemejwe na immunoblotting na PCR nyayo.Imikorere ya Mitochondrial yasesenguwe no gupima a) ibikorwa byibanze bya mitochondial, b) umusaruro wa anion ya superoxide na c) imikorere yumuntu ku giti cye cyurwego rutandukanye rwurwego rwubuhumekero.Twabonye ko kuvuga birenze urugero PG gutanga lentivi ral gene biganisha kuri a kugabanuka k'igipimo cyo gukwirakwizwa no ku busembwa mu bushobozi bwa adipogenic ugereranije no kugenzura.Isesengura ryinshi rya proteomics ryerekanye poroteyine 181 ku buryo bugaragara (p <0.05) zahinduwe muri PG-zerekana preadipocytes.Imikorere ya Mitochondrial yangiritse muri selile-selile.By'umwihariko, twabonye ubwiyongere bwibikorwa bya complexe I hamwe n’umusaruro mwinshi wa anion ya Superoxide.Inkubasi hamwe nubwoko bwa Oxygene (ROS) ikora scavenger itera kugabanuka kwa proteolysis ya autophagic nkuko byagaragajwe na LC3-II / LC3-I. Imvugo ya PG muri selile 3T3L1 iteza impinduka muburyo butandukanye bwibinyabuzima, harimo imiterere ya cytoskeleton, metabolisme ya lipide, calcium amabwiriza, ubusemuzi, kuzuza poroteyine no kubyara ingufu na mitochondria.Amakuru yacu ashimangira uruhare rwo kwegeranya ROS kuri phenotype yo gusaza imburagihe no gushyiraho isano hagati yimikorere mibi ya mitochondrial no gutakaza proteostasis muri HGPS.