The novel squamosamide derivative (compound FLZ) attenuated 1-methyl, 4-phenyl-pyridinium ion (MPP+)-induced apoptosis and alternations of related signal transduction in SH-SY5Y cells.
Compound FLZ (cFLZ) is a synthetic novel derivative of natural squamosamide. Previous pharmacological study found that cFLZ improved the abnormal behavior and the decrease of dopamine content in striatum in 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) model mice. 1-Methyl 4-phenylpyridinium (MPP+) is the active metabolite of MPTP to cause Parkinsonism in experimental animals. The purpose of this paper was to further study the protective action of cFLZ against MPP+-induced apoptosis and alternations of related signaling transduction. The results indicated that cFLZ at concentrations of 0.1 microM and 1 microM prevented 100 microM MPP+-induced apoptosis of SH-SY5Y cells, and inhibited the release of cytochrome C and apoptosis-inducing factor (AIF), and the activation of caspase 3 and NF-kappaB as well as alpha-synuclein gene and protein expressions. The results suggest that cFLZ possesses potent neuroprotective activity and may be a potential anti-Parkinson's disease drug worthy for further study.
Zhang
Dan
D
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Zhang
Jian-Jun
JJ
Liu
Geng-Tao
GT
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D044482:Benzeneacetamides / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma; D009498:Neurotoxins / Q000494:pharmacology*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
D044482:Benzeneacetamides; D009498:Neurotoxins; D010636:Phenols; D012333:RNA, Messenger; D051844:alpha-Synuclein; C084439:squamosamide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D053148:Caspase 3