HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

FLZ, a novel HSP27 and HSP70 inducer, protects SH-SY5Y cells from apoptosis caused by MPP(+).

Abstract
Heat shock proteins (HSPs) play an essential role in various neurodegenerative diseases. Manipulation of upregulation of HSPs in cells has been demonstrated to provide a therapeutic strategy to counteract the misfolding and aggregation of proteins that resulted in neurodegenerative disease. Our previous studies have shown that FLZ, a synthetic novel derivative of squamosamide from a Chinese herb, had potent neuroprotective effect against several experimental Parkinson's disease (PD) models. However, the mechanism of its neuroprotective effect is still not clarified. The present study demonstrated that FLZ induced HSP27 and HSP70 proteins and mRNA expression in a time- and dose-dependent manner in SH-SY5Y cells. Further studies showed that FLZ treatment stimulated the activation of heat shock factor 1 (HSF1) and its regulatory kinase Akt. Inactivation of Akt pathway by the PI3K inhibitor LY294002 blocked the expression of HSP27 and HSP70 induced by FLZ. Moreover, the inducing effects of FLZ on HSP27, HSP70, and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/HSP70 induced by FLZ against MPP(+) was assessed in SH-SY5Y cells. The pretreatment of FLZ significantly induced the accumulations of HSP27/HSP70 and suppressed the apoptosis caused by MPP(+) in SH-SY5Y cells. However, the protective effects of FLZ against MPP(+) were significantly blocked by quercetin, which indicated that the cytoprotective action of FLZ against MPP(+)-induced apoptosis is at least partially mediated by its induction of HSP27/HSP70. These results provide new evidence for elucidating the mechanism of the neuroprotective effect of FLZ against PD.
AuthorsXiang-Chen Kong, Dan Zhang, Cheng Qian, Geng-Tao Liu, Xiu-Qi Bao
JournalBrain research (Brain Res) Vol. 1383 Pg. 99-107 (Apr 06 2011) ISSN: 1872-6240 [Electronic] Netherlands
PMID21295016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Benzeneacetamides
  • DNA-Binding Proteins
  • HSF1 protein, human
  • HSP27 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Neuroprotective Agents
  • Phenols
  • Transcription Factors
  • squamosamide
  • Eosinophil-Derived Neurotoxin
  • 1-Methyl-4-phenylpyridinium
Topics
  • 1-Methyl-4-phenylpyridinium (toxicity)
  • Apoptosis (drug effects)
  • Benzeneacetamides (pharmacology)
  • Blotting, Western
  • Cell Line
  • DNA-Binding Proteins (drug effects, metabolism)
  • Electrophoretic Mobility Shift Assay
  • Enzyme Activation (drug effects)
  • Eosinophil-Derived Neurotoxin (toxicity)
  • HSP27 Heat-Shock Proteins (biosynthesis)
  • HSP70 Heat-Shock Proteins (biosynthesis)
  • Heat Shock Transcription Factors
  • Humans
  • Microscopy, Fluorescence
  • Neurons (drug effects)
  • Neuroprotective Agents (pharmacology)
  • Phenols (pharmacology)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors (drug effects, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: