A pro-survival effect of polyamine depletion on norepinephrine-mediated apoptosis in cardiac cells: role of signaling enzymes |
| |
Authors: | Silvia Cetrullo Benedetta Tantini Annalisa Facchini Carla Pignatti Claudio Stefanelli Claudio Marcello Caldarera Flavio Flamigni |
| |
Institution: | (1) Department of Biochemistry “G. Moruzzi”, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy;(2) National Institute for Cardiovascular Research, Bologna, Italy; |
| |
Abstract: | Recent studies report that the primary transmitter of sympathetic nervous system norepinephrine (NE), which is actively produced
in failing human heart, is able to induce apoptosis of rat cardiomyocytes. Apoptotic cell death of cardiomyocytes is involved
in several cardiovascular diseases including ischemia, hypertrophy and heart failure, therefore representing a potential therapeutic
target. The natural occurring polyamines, putrescine, spermidine and spermine, are biogenic amines involved in many cellular
processes, including apoptosis. Thus, we have studied the involvement of polyamines in the apoptosis of cardiac cells induced
by the treatment with NE. The results indicate that NE caused an early induction of the activity of ornithine decarboxylase
(ODC), the first enzyme in polyamine biosynthesis, followed by a later increase of apoptotic cell death. This effect was prevented
in the presence of α-difluoromethylornithine, an irreversible inhibitor of ODC. Moreover, the study of some key signal transduction
pathways revealed an involvement of AMP-activated protein kinase, AKT and p38 mitogen-activated protein kinases, in the modulation
by polyamines of the response of cardiomyocytes to NE. In fact, polyamine-depleted cells showed an altered activation pattern
of these kinases that may contrast apoptosis and appeared to result from a differential effect on the specific phosphatases
that dephosphorylate and switch off these signaling proteins. In conclusion, these results indicate that in cardiac cells
polyamines are involved in the execution of the death program activated by NE, and suggest that their apoptosis facilitating
action is mediated by a network of specific phosphatases and kinases. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|