Lao Y

References (2)

Title : Mitochondrial proteomic analysis and characterization of the intracellular mechanisms of bis(7)-tacrine in protecting against glutamate-induced excitotoxicity in primary cultured neurons - Fu_2007_J.Proteome.Res_6_2435
Author(s) : Fu H , Li W , Liu Y , Lao Y , Liu W , Chen C , Yu H , Lee NT , Chang DC , Li P , Pang Y , Tsim KWK , Li M , Han Y
Ref : J Proteome Res , 6 :2435 , 2007
Abstract : Increasing evidence supports that the mitochondrial dysfunction, mainly caused by abnormal changes in mitochondrial proteins, plays a pivotal role in glutamate-induced excitotoxicity, which is closely associated with the pathogenesis of acute and chronic neurodegenerative disorders, such as stroke and Alzheimer's disease. In this study, post-treatment of cerebellar granule neurons with bis(7)-tacrine significantly reversed declines in mitochondrial membrane potential, ATP production, and neuronal cell death induced by glutamate. Moreover, this reversal was independent of NMDA antagonism, acetylcholinesterase inhibition, and cholinergic pathways. Using two-dimensional differential in-gel electrophoresis, we conducted a comparative analysis of mitochondrial protein patterns. In all, 29 proteins exhibiting significant differences in their abundances were identified in the glutamate-treated group when compared with the control. The expression patterns in 22 out of these proteins could be reversed by post-treatment with bis(7)-tacrine. Most of the differentially expressed proteins are involved in energy metabolism, oxidative stress, and apoptosis. In particular, the altered patterns of four of these proteins were further validated by Western blot analysis. Our findings suggest that multiple signaling pathways initiated by the altered mitochondrial proteins may mediate glutamate-induced excitotoxicity and also offer potentially useful intracellular targets for the neuroprotection provided by bis(7)-tacrine.
ESTHER : Fu_2007_J.Proteome.Res_6_2435
PubMedSearch : Fu_2007_J.Proteome.Res_6_2435
PubMedID: 17530875

Title : Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating L-type calcium channels - Fu_2006_J.Neurochem_98_1400
Author(s) : Fu H , Li W , Lao Y , Luo J , Lee NT , Kan KK , Tsang HW , Tsim KWK , Pang Y , Li Z , Chang DC , Li M , Han Y
Ref : Journal of Neurochemistry , 98 :1400 , 2006
Abstract : Beta amyloid protein (Abeta) and acetylcholinesterase (AChE) have been shown to be closely implicated in the pathogenesis of Alzheimer's disease. In the current study, we investigated the effects of bis(7)-tacrine, a novel dimeric AChE inhibitor, on Abeta-induced neurotoxicity in primary cortical neurons. Bis(7)-tacrine, but not other AChE inhibitors, elicited a marked reduction of both fibrillar and soluble oligomeric forms of Abeta-induced apoptosis as evidenced by chromatin condensation and DNA specific fragmentation. Both nicotinic and muscarinic receptor antagonists failed to block the effects of bis(7)-tacrine. Instead, nimodipine, a blocker of L-type voltage-dependent Ca2+ channels (VDCCs), attenuated Abeta neurotoxicity, whereas N-, P/Q- or R-type VDCCs blockers and ionotropic glutamate receptor antagonists did not. Fluorescence Ca2+ imaging assay revealed that, similar to nimodipine, bis(7)-tacrine reversed Abeta-triggered intracellular Ca2+ increase, which was mainly contributed by the extracellular Ca2+ instead of endoplasmic reticulum and mitochondria Ca2+. Concurrently, using whole cell patch-clamping technique, it was found that bis(7)-tacrine significantly reduced the augmentation of high voltage-activated inward calcium currents induced by Abeta. These results suggest that bis(7)-tacrine attenuates Abeta-induced neuronal apoptosis by regulating L-type VDCCs, offers a novel modality as to how the agent exerts neuroprotective effects.
ESTHER : Fu_2006_J.Neurochem_98_1400
PubMedSearch : Fu_2006_J.Neurochem_98_1400
PubMedID: 16771827