JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis.

Trophic factor deprivation (TFD) activates c-Jun N-terminal kinases (JNKs), culminating in coordinate AP1-dependent transactivation of the BH3-only BCL-2 proteins BIM(EL) and HRK, which in turn are critical for BAX-dependent cytochrome c release, caspase activation, and apoptosis. Here, we report that TFD caused not only induction but also phosphorylation of BIM(EL). Mitochondrially localized JNKs but not upstream activators, like mixed-lineage kinases (MLKs) or mitogen-activated protein kinase kinases (MKKs), specifically phosphorylated BIM(EL) at Ser65, potentiating its proapoptotic activity.

Myosin from failing and non-failing human ventricles exhibit similar contractile properties.

In non-failing human myocardium, V1 myosin comprises a small amount (<10%) of the total myosin content, whereas end-stage failing hearts contain nearly 100% V3 myosin. It has been suggested that this shift in V1 myosin isoform content may contribute to the contractile deficit in human myocardial failure. To test this hypothesis, myosin was isolated from human failing and non-failing ventricles, and non-failing atria.

Cardiac troponin T isoforms demonstrate similar effects on mechanical performance in a regulated contractile system.

Alteration of troponin T (TnT) isoform expression has been reported in human and animal models of myocardial failure. The two adult beef cardiac TnT isoforms (TnT(3) and TnT(4)) were isolated for comparative functional analysis. Thin filaments were reconstituted containing pure populations of the isoforms.