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Glutathione depletion and cardiomyocyte apoptosis in viral myocarditis
Author(s) -
Kytö V.,
Lapatto R.,
Lakkisto P.,
Saraste A.,
VoipioPulkki L.M.,
Vuorinen T.,
Pulkki K.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01313.x
Subject(s) - viral myocarditis , apoptosis , glutathione , myocarditis , tunel assay , oxidative stress , biology , microbiology and biotechnology , andrology , immunology , endocrinology , medicine , biochemistry , enzyme
Background The course of viral myocarditis is highly variable. Oxidative stress and Bcl‐2 family genes may play a role in its pathogenesis by regulating the amount of cardiomyocyte apoptosis. Apoptosis is difficult to detect and quantify in vivo . Therefore, we set to look for indicators of this potentially preventable form of cell death during various phases of experimental murine coxsackievirus B3 myocarditis. Methods BALB/c mice were infected with the cardiotropic coxsackievirus B3 variant. Glutathione (HPLC), cardiomyocyte apoptosis (TUNEL and caspase‐3 cleavage), Bax and Bcl‐X L mRNA expression (real time RT‐PCR), histopathology and viral replication (plaque assay and real time RT‐PCR) were measured from day 3 to day 20 after infection. Results Infection caused severe myocarditis and led to progressive decrease of plasma glutathione levels. Myocardial mRNA levels of pro‐apoptotic Bax and antiapoptotic Bcl‐X L were significantly increased from day 3 onwards. Bax mRNA and ratio of Bax to Bcl‐X L correlated with cardiomyocyte apoptosis ( r = 0·77, P = < 0·001 and r 0·51, P < 0·01, respectively). Cardiomyocyte apoptosis was highest on day 5, coinciding with a rapid decline in plasma glutathione ( r = −0·52, P = 0·003). Conclusions Systemic oxidative stress as indicated by decreased plasma glutathione levels coincides with cardiomyocyte apoptosis in experimental coxsackievirus myocarditis. Decreased plasma glutathione levels and changes in cardiac Bax and Bcl‐X L mRNA expression identify a phase of myocarditis in which the potentially preventable cardiomyocyte apoptosis is mostly observed.