AIMS: Loss of cardiac muscle by programmed cell @entity204 contributes to the progression of @entity741 . @entity519 , metabolite waste buildup and energy depletion are components of @entity63 which may initiate caspase dependent and independent cell @entity204 pathways. Previous work from our laboratory has shown that combined @entity519 with @entity520 , a hallmark of @entity63 promotes @entity299 with increasing severity as the pH declines. @entity519 - @entity520 was demonstrated to activate the pro-apoptotic Bcl-2 protein @entity34714 which initiated opening of the mitochondrial permeability transition pore and cell @entity204 in the absence of caspase activation. Because calpains are known to contribute to @entity63 @entity296 in some models, we hypothesized that they are intermediates in the @entity34714 -mediated @entity204 caused by @entity519 - @entity520 . MAIN METHODS: Neonatal @entity35 cardiac myocytes were subjected to @entity519 with and without @entity520 and the contribution of calpains to @entity519 - @entity520 cell @entity204 determined. KEY FINDINGS: Here we report that the @entity204 pathway activated by @entity519 - @entity520 is driven by a combination of @entity460 -activated calpains and pro- @entity204 factors (DNases) secreted by the mitochondria. Cytochrome c accumulated in the cytoplasm during @entity519 - @entity520 but caspase activity was repressed through a calpain-dependent process that prevents the cleavage of procaspase 3. Calpain inhibitors provide vigorous protection against @entity519 - @entity520 -induced programmed @entity204 . Knockdown of @entity34714 with siRNA prevented calpain activation confirming a central role of @entity34714 in this pathway. SIGNIFICANCE: The results implicate @entity34714 and calpain as dependent components of @entity204 caused by @entity519 - @entity520 .

@entity34714 promotes XXXX and @entity204 .

@entity34714 :: ('84480(Tax:10116)', 'Gene') :: ['BNIP3'] @entity296 :: ('MESH:D009202', 'Disease') :: ['myocardial damage'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia', 'ischemic'] @entity520 :: ('MESH:D000138', 'Disease') :: ['acidosis'] @entity519 :: ('MESH:D000860', 'Disease') :: ['Hypoxia', 'hypoxia'] @entity741 :: ('MESH:D017202', 'Disease') :: ['ischemic heart disease'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac myocyte injury'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death', 'cardiac myocyte death']
@entity460 :: (MESH:D002118,Chemical) :: ['calcium']
