Physiological stresses (heat, hemodynamics, genetic mutations, oxidative injury and myocardial ischemia) produce pathological states in which protein damage and misfolded protein structures are a common denominator. The specialized proteins family of antistress proteins - molecular chaperons (HSPs) - are responsible for correct protein folding, dissociating protein aggregates and transport of newly synthesized polypeptides to the target organelles for final packaging, degradation or repair. They are inducible at different cell processes such as cell division, apoptosis, signal transduction, cell differentiation and hormonal stimulation. HSPs are involved in numerous diseases including cardiovascular pathologies, revealing changes of expression and cell localization. We studied the possible changes in expression level of abundant mitochondrial chaperon Hsp60 and main human cytochrome P450 monooxygenase (2E1 isoform) at dilated cardiomyopathy (DCM) progression at the end stage of heart failure using Western blot analysis. The ischemic and normal humans' hearts were studied as control samples. We observed the decrease of Hsp60 level in cytoplasmic fraction of DCM- and ischemia-affected hearts' left ventricular and significant increase of Hsp60 in mitochondrial fractions of all hearts investigated. At the same time we detected the increase of P450 2E1 expression level in ischemic and dilated hearts' cytoplasmic fractions in comparison with normal myocardium and no detectable changes in microsomal fractions of hearts investigated which could be linked with increased level of oxidative injury for DCM heart muscle. In addition, all the changes described are accompanied by significant decrease of ATPase activity of myosin purified from DCM-affected heart in comparison with normal and ischemic myocardia as well. The data obtained allow us to propose a working hypothesis of functional link between antistress (HSPs) and antioxidative (cytochromes) systems at DCM progression.
Äîñë³äaeå íî çì³íè ê³ëüê³ñíî ãî ð³âíÿ ìî ëå êó ëÿð íî ãî øà ïå ðî íó Hsp60 ó òêà íèí³ ñåð öÿ ïðè äè ëÿ-òàö³éí³é êàðä³îì³îïàò³¿ (ÄÊÌÏ). Âè ÿâ ëå íî çðîñ òàí íÿ ñó ìàð íî ãî âì³ñòó Hsp60 ÿê ó ë³çà òàõ òêà íèíè ñåð äåöü ëþ äåé, õâî ðèõ íà ÄÊÌÏ, òàê ³ â ë³çà òàõ òêà íèí ñåð äåöü ìè øåé ³ç åê ñïå ðè ìåí òàëü íèì çà õâîðþ âàí íÿì, ïîä³áíèì äî ÄÊÌÏ ëþ äè íè. Âïåð øå âñòà íîâ ëå íî çá³ëüøåí íÿ ê³ëüêîñò³ Hsp60 ó ì³òî-õîíäð³àëüí³é ôðàêö³¿ òà çíè aeåí íÿ ó öè òîï ëàç ìà òè÷í³é, ùî ìîaeå áóòè îäíèì ³ç ÷èí íèê³â àïîï òî çó êàðä³îì³îöèò³â ïðè ñåð öåâ³é íå äîñ òàò íîñò³, âèê ëè êàí³é 䳺þ õðîí³÷íî ãî ñòðå ñó. Çà ðå çóëü òà òà ìè ³ìó íîã³ñòîõ³ì³÷íî ãî àíàë³çó ñåð äåöü ìè øåé ³ç åê ñïå ðè ìåí òàëü íîþ ïà òî ëî㳺þ, ïîä³áíîþ äî ÄÊÌÏ ëþ äè íè, ïî êà çà íî, ùî ï³äâè ùåí íÿ ê³ëüê³ñíî ãî ð³âíÿ Hsp60 ó òêà íèí³ ñåð öÿ íî ñèòü íå îäíîð³äíèé õàðàê òåð: çíà÷ íå çðîñ òàí íÿ â³äáó âàºòüñÿ ëèøå â îêðå ìèõ êàðä³îì³îöè òàõ, éìîâ³ðíî, â òèõ, äå àê òè âî-âàí³ àí òèñ òðå ñîâ³ ìå õàí³çìè çà õèñ òó êë³òèíè â³ä 䳿 õðîí³÷íî ãî ñòðå ñó. Êëþ ÷îâ³ ñëî âà: ìî ëå êó ëÿðí³ øà ïå ðî íè, Hsp60, äè ëÿ òàö³éíà êàðä³îì³îïàò³ÿ, êàðä³îì³îöèò, àïîï òîç.
Recently, it has been suggested that some heat shock proteins such as Hsp70 and Hsp60 are involved in autoimmune diseases including cardiospecific ones. In this work we focused on the involvement of another wellknown heat shock protein, Hsp90, and its novel co-chaperone,Sgt1, in dilated cardiomyopathy (DCM). We found that the level of autoantibodies against these two proteins was significantly higher in patients with DCM and ischemic heart disease than in sera of healthy donors. We have also analyzed the expression level and subcellular localization of Hsp90 and Sgt1 in diseased myocardia. Using Western blot we found changes in subcellular localization of Hsp90 in the left ventricle of DCM hearts while the total level of this protein remained unchanged. Regarding the Sgt1 protein, we found an increased level in DCM and no changes in subcellular localization. Taken together, our data suggest that Hsp90 and Sgt1 might be involved in the progression of heart failure and might serve as markers for cardiomyopathies of different origin.
Институт молекулярной биологии и генетики НАН Украины 252143, Киев, ул. Академика Заболотного, 150 При системных аутоиммунных заболеваниях выявляются аутоантитела против многих белков и рибонуклеопротеидов-компонентов аппарата трансляции. Ранее нами было сообщено о выявлении аутоантител против серил-тРНК синтетазы у больных системной красной волчанкой и ревматоидным артритом. В данной работе нами охарактеризованы аутоантитела против другого компонента аппарата трансляции-тирозил-тРНК синтетазы. В то время как поликлональные антитела ингибировали аминоацилирующую активность фермента до 30% базового уровня, аутоантитела из аутоиммунных сывороток активировали фермент до 280 % базового уровня, чего не наблюдалось для других исследованных в этом направлении аминоацил-тРНК синтетаз. Обсуждаются возможные причины подобного феномена.
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