Nakai Masamichi [a]. Hojo Kaori. Taniguchi Taizo. Terashima Akira.
Kawamata Toshio. Hashimoto Takeshi. Maeda Kiyoshi. Tanaka Chikako.
PKC and tyrosine kinase involvement in amyloid beta (25-35)-induced
chemotaxis of microglia, Neuroreport 9(15) :3467-3470, 1998.
Abstract
Microglia are activated by amyloid beta (Abeta) in vivo and
in vitro, and Abeta-activated microglia may be involved in
the pathogenesis of Alzheimer's disease (AD). We investigated the mechanism
of microglial chemotaxis induced by Abeta
(25-35), an active fragment of Abeta. Abeta (25-35) 0.1 and 1 nM stimulated
microglial chemotaxis. The protein kinase C
(PKC) inhibitors chelerythrine (0.5 and 2 muM), calphostin C (1 muM)) and
staurospine (10 nM) significantly inhibited the microglial
chemotaxis induced by Abeta (25-35) (1 nM). The chemotactic
effect of Abeta (25-35) on microglia was desensitized by
pretreatment of microglia with 1 ng/ml
12-O-tetradecanoylphorbol 13-acetate (TPA). Pretreatment of cells with Abeta
(25-35) (1 nM) also desensitized the chemotactic effect by Abeta (25-35) (1
nM). The desensitization by TPA or Abeta (25-35) was inhibited when
staurosporine was present in the pretreatment media. The tyrosine kinase
inhibitor herbimycin A (0.1 and 1 muM) significantly inhibited the
microglial chemotaxis induced by Abeta
(25-35) (1 nM). Based on these observations, it seems likely that PKC and
tyrosine kinase are involved in the Abeta-induced chemotaxis
of microglia.
Return to Chemotaxis References.