title: PP2 and piceatannol inhibit PrP106-126-induced iNOS activation mediated by CD36 in BV2 microglia.
abstract: Prion diseases are a group of transmissible fatal neurodegenerative disorders of humans and animals, including bovine spongiform encephalopathy, scrapie, and Creutzfeldt-Jakob disease. Microglia, the resident macrophages of the central nervous system, are exquisitely sensitive to pathological tissue alterations, altering their morphology and phenotype to adopt a so-called activated state and perform immunological functions in response to pathophysiological brain insults. Although recent findings have provided valuable insights into the role microglia play in the proinflammatory events observed in prion, the intracellular signaling molecules responsible for the initiation of these responses remain to be elucidated. It seems that microglial activation involve PrP106-126 binding and the activation of cell surface immune and adhesion molecules such as CD36 and integrins, with the subsequent recruitment of Src family tyrosine kinases such as Fyn, Lyn, and Syk kinases. In the present study, we show that CD36 is involved in PrP106-126-induced microglial activation and that PP2 and piceatannol (Pic) can abrogate neurotoxic prion peptides-induced inducible nitric oxide synthase activation in microglia. These findings unveil a previously unrecognized role of PP2 and Pic as Src family kinase Fyn and the tyrosine kinase Syk inhibitor involved in neurotoxic prion peptides-microglia interactions, thus providing new insights into mechanisms underlying the activation of microglia by neurotoxic prion peptides.
authors.affiliation: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Siming
authors.initials: S
authors.lastname: Zhang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kouadir
authors.forename: Rongrong
authors.initials: R
authors.lastname: Tan
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Chang
authors.forename: Binrui
authors.initials: B
authors.lastname: Xu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yin
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011328:Prions / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: C412373:AG 1879; D018955:CD36 Antigens; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011328:Prions; D011743:Pyrimidines; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; C041525:3,3',4,5'-tetrahydroxystilbene; D052247:Nitric Oxide Synthase Type II; D019061:src-Family Kinases
keywords: PrP106–126; bv2 microglia; cd36; iNOS; piceatannol (Pic); pp2