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.

No abstract

Experimental model of autoimmune myosin-induced injury of BALB/c mouse myocardium, similar to human dilated cardiomyopathy (DCM), has been developed. The immunisation by myosin, purified from DCM-affected human heart initiated the following DCM-like myocardial damage: myocytolysis, cardiosclerosis, thinning of left ventricular wall, changes in cardiac actomyosin ATP-ase activity and increase of anti-myosin autoantibodies level.

The autoantibodies directed against actin and myosine have been detected in the blood sera of patients with dilated cardiomyopathy (DCMP) at the level that was sufficiently higher than in healthy donors. While comparing of the immunogeneicity of these pro teins we have stated that myosine from affected by DCMP myocardium have been more immunogenic then from normal one. In the case of actin the immunogeneicity have been higher for the protein from normal myocard. The investigations of actin by limited proteolysis may suggest that the differencies in immune properties are not connected with primary structure but with structures of higher levels.