Señalización celular y expresión génica

HARNICHAR E; SANTALLA M; VALVERDE CA; MATTIAZZI A; FERRERO P

C.A.B.A

Congreso; SAIB Molecular Mechanisms in cell signaling and gene expression; 2013

SAIB

We use Drosophila melanogaster for studying cardiac diseases.One transgenic strain containing a fluorescent reporter system thatsenses intracellular twitch Ca2+ transient increases was utilized. Weobserved changes in the frequency of Ca2+ transients with age insemi-intac fly heart preparations and its putative modification by1) The inhibition of Ca2+-calmodulin-dependent protein kinase(CaMKII), involved in Ca2+ cycling and 2) the reduction in eIF4Eexpression, an eukaryotic translation initiation factor. Results: Fliesbetween 60 and 70 days old showed reduction of heart rate comparedwith 7 days old flies and widespred distribution of cardiac periods(intervals between transient increases of Ca2+). Arrhythmicity index(standard deviation of the heart period), increased from 0.27 to0.52 (n=12). CaMKII inhibition reduced dispersion of cardiacperiods distribution and arrhythmicity index from 0.27 to 0.19 (n =21). Lower levels of eIF4E reduced dispersion of cardiac periodsdistribution and arrhythmicity index from 0.27 to 0.09 in 7 daysold (n=18) flies. The results indicate that CaMKII regulates cardiacfunction in Drosophila and is an arrhythmogenic molecule. Moreimportant, eIF4E participates in the genesis of arrhythmiasindependently of its canonical function as translation factor, pointingto this factor as a putative new candidate involved in thepathophysiology of the mammalian heart.