Molecular chaperone, HSP60, and cytochrome P450 2E1 co-expression in dilated cardiomyopathy.
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.
Sidorik
L
L
Institute of Molecular Biology and Genetics, NAS of Ukraine, 150 Zabolotnogo street, 03143, Kiev-143, Ukraine. sidorik@imbg.org.ua
Kyyamova
R
R
Bobyk
V
V
Kapustian
L
L
Rozhko
O
O
Vigontina
O
O
Ryabenko
D
D
Danko
I
I
Maksymchuk
O
O
Kovalenko
V N
VN
Filonenko
V V
VV
Chaschin
N A
NA
D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000503:physiopathology; D018834:Chaperonin 60 / Q000096:biosynthesis*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D015870:Gene Expression; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000096:biosynthesis
D018834:Chaperonin 60; D019392:Cytochrome P-450 CYP2E1; D009218:Myosins