Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons.

A stress-activated protein kinase pathway comprising mitogen-activated protein kinase kinases (MKKs), c-Jun N-terminal kinase (JNK) and the transcription factor c-Jun is implicated in neuronal apoptosis. Using an immune-complex kinase assay, we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced apoptosis of rat cerebellar granule neurons (CGN). MKK7, but not MKK4, was activated within the first 4-6 h in four independent sets of 14-h CGN apoptosis time-courses.

The pharmacology of apoptosis.

Apoptosis is an area of intense scientific interest, which encompasses the study of and triggers mechanisms involved in mediating the cell biology of programmed cell death. A number of low molecular weight compounds have been used to inhibit or enhance this fundamental cellular process and so apoptosis has now become amenable to pharmacological manipulation. In this review Ross Kinloch, Mark Treherne, Mike Furness and Iradj Hajimohamadreza will focus on the current literature describing the pharmacology of apoptosis, with particular reference to the therapeutic potential that could arise from the development of pro- and anti-apoptotic drugs.

Intrasynaptosomal free calcium concentration is increased by phorbol esters via a 1,4-dihydropyridine-sensitive (L-type) Ca2+ channel.

Incubation of non-depolarised fura-2-loaded rat cortical synaptosomes with 12-tetradecanoylphorbol-13-monoacetate (TPA) results in a dose-dependent increase in calcium concentration (to a maximum of 140%). It is dependent on extrasynaptosomal Ca2+, is partially blocked by 1 microM verapamil and effectively blocked by 100 microM verapamil (greater than or equal to 90%). Nifedipine (1 microM), nicardipine (1 microM) and omega-conotoxin fraction GVIA from Conus geographus (50 nM) (omega-CgTx) also cause blockade (greater than or equal to 90%) of the increase.