hrvatski

Polimorfizmi stresnih proteina i KOPB

Stresni proteini (Hsp) pripadaju skupini unutarstaničnih proteina koji imaju sposobnost stabilizacije nepravilno strukturiranih proteina i peptida, čime promoviraju preživljenje, te inhibiraju programiranu staničnu smrt. Geni koji kodiraju za članove porodice stresnih proteina (Hsp70), hsp70-1, hsp70-2 i hsp70-hom smješteni su unutar gena klase III sustava tkivne kompatibilnosti (MHC). U skladu s njihovim smještajem u genomu istraživana je povezanost polimorfizama ovih gena s različitim bolestima čija se pojavnost zasniva na poremećenoj funkciji imunološkog sustava. U skladu sa šaperonskom ulogom stresnih proteina istraživana je i povezanost istih polimorfizama s neravnotežom oksidativnih/anti-oksidativnih spojeva u organizmu. Kako je poznato da u patogenezi kronične opstrukcijske plućne bolesti (KOPB) oksidativno/antioksidatvini putevi imaju važnu ulogu, ispitivali smo polimorfizme duljine restrikcijskih fragmenata gena hsp70-2 i hsp70-hom, izlaganjem fragmenata DNA dobivenih umnažanjem genskog slijeda reakcijom lančane reakcije polimeraze, djelovanju restrikcijskih endonukleaza. Nismo uočili statistički značajnu razliku u raspodjeli A/G(+1267) polimorfizma u kodirajućoj regiji gena hsp70-2, kao ni u raspodjeli T/C (+2437) polimorfizma u kodirajućoj regiji gena hsp70-hom između zdravih ispitanika i ispitanika s KOPB. Hsp32 gen (HMOX-1) kodira za mali stresni protein 32 (Hsp32 ili hem oksigenaza-1), enzim koji katalizira razgradnju hema do biliverdina u procesu koji osigurava zaštitu stanicama od oštećenja uzrokovanih oksidativnim radikalima. U populaciji se polimorfizam ovog gena pojavljuje u obliku različitog broja GT ponavljanja u promotorskoj regiji gena odogovornoj za ekspresiju gena i moguću indukciju aktivnosti ovog enzima u stanjima oksidativnog stresa. Između zdravih ispitanika i ispitanika s KOPB nismo uočili statistički značajnu razliku u broju GT ponavljanja hsp32 (HMOX-1) gena. Heat shock proteins are intracellular proteins with ability to stabilize missfolded proteins and peptides, thereby promoting cell survival and preventing programmed cell death. Genes encoding members of the heat shock protein (Hsp70) family hsp70-1, hsp70-2 i hsp70-hom lie in the class III region of the human major histocompatibility complex (MHC). Relating to their location, polymorphisms of these genes were analyzed in association with occurence of different diseases with immune component. Relating to their chaperone role polymorphisms of these genes were also analyzed in association with an oxidative/antioxidative imbalance. In the pathogenesis of chronic obstructive lung disease (COPD) oxidative/antioxidative pathways play important role. Therefore we studied hsp70-2 and hsp70-hom gene polymorphisms using restriction fragment length polymorphism – polymerase chain reaction method (RFLP-PCR). The obtained data showed that there were no statistically significant difference in A/G(+1267) polymorphism distribution in the coding region of hsp70-2, as well as in T/C (+2437) polymorphism distribution in the coding region of hsp70-hom between healthy individuals and patients with COPD. Hsp32 gene (HMOX-1) encodes for small heat shock protein 32 (Hsp32 or heme oxygenase-1), enzyme that catalyzes the degradation of heme to biliverdin in a reaction which provides cells with protection in oxidative mediated injury. Polymorphism of this gene is presented in the number GT repeats in 5'-flanking region responsible for gene expression and plausible enzyme induction in oxidative stress conditions. The obtained data showed that there was no statistically significant difference in hsp32 gene polymorphism between between healthy individuals and patients with COPD.

stresni proteini; polimorfizam; KOPB

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