title: SpeedyRINGO inhibits calpain-directed apoptosis in neurons.
abstract: The calcium-activated proteolytic enzyme calpain is one of the key proteins that can directly or indirectly drive neurons into apoptosis. The indirect way is through cyclin dependent kinase 5 (CDK5), a non-mitotic kinase, which is upregulated through calpain overactivation and followed by a subsequent increase in p53 and active caspase-3 levels under neurodegenerative conditions. The direct way is the upregulation of p53 by calpain itself, since p53 is a substrate for it. SpeedyRINGO is an atypical cell cycle regulator that has been shown to have protective effects in mitotic cells against apoptosis by inhibiting caspase-3 activation when p53 is present. Our aim was to reveal possible protective effects of SpeedyRINGO against calpain-induced caspase-3 activation in neurons which is crucial in terms of providing novel insights in preventing the caspase-3 activation cascade in neurodegeneration. For this reason, mRNA and protein levels were analyzed by qRT-PCR, western blotting, and immunofluorescence. We show that calpain overactivation leads to the upregulation of p53 and a subsequent increase in active caspase-3 level, indicating activation of apoptotic machinery in neurons. This calpain-directed caspase-3 activation upon upregulation of p53 is inhibited by the expression of SpeedyRINGO in rat hippocampal neurons. Therefore, SpeedyRINGO acts as a savior for neurons that are under apoptosis due to caspase-3 activation.
authors: Department of Molecular Biology and Genetics, Istanbul Technical University, Maslak, Istanbul, Turkey.
authors: Aysegul
authors: A
authors: Yildiz-Unal
authors: Sirin
authors: S
authors: Korulu
authors: Arzu
authors: A
authors: Karabay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C486530:SPDYA protein, human; D002154:Calpain