Rat Alpha(1)-macroglobulin Enhances Nerve Growth Factor-promoted Neurite Outgrowth, Trka Phosphorylation, And Gene Expression Of Pheochromocytoma Pc12 Cells

Rat Alpha(1)-macroglobulin Enhances Nerve Growth Factor-promoted Neurite Outgrowth, Trka Phosphorylation, And Gene Expression Of Pheochromocytoma Pc12 Cells

Lee P G; Koo P H

Journal of Neurochemistry

2000

2000-01

Monoamine-activated human alpha(2)-macroglobulin (alpha(2)M) has been previously demonstrated to inhibit TrkA-, TrkB-, and TrkC-mediated signal transduction. Rat alpha(1),-macroglobulin (alpha(1)M) and alpha(2)M are structural homologues of human alpha(2)M, but rat alpha(1)M is distinctly different from rat alpha(2)M in many ways and its role in the mammalian nervous system is unknown. In this report, monoamine-activated rat alpha(1)M was demonstrated to enhance in a dose-dependent manner nerve growth factor (NGF)-promoted neurite outgrowth in pheochromocytoma PC12 cells. Monoamine-activated alpha(1)M by itself, however, was neither neurotrophic nor mitogenic to PC12 cells. To investigate further its possible mode of action, the ability of monoamine-activated alpha(1)M and normal alpha(1)M to bind and to activate the NGF receptor (TrkA) was investigated. Monoamine-activated alpha(1)M formed a more stable complex with TrkA than normal alpha(1)M, but the binding of mono-amina-activated alpha(1)M to TrkA was adversely affected by prior stimulation of TrkA with NGF. In addition, monoamine-activated alpha(1)M enhanced the NGF-promoted TrkA phosphorylation and up-regulated the expression of NGF-inducible immediate-early genes (c-jun and NGFI-A) and delayed-response genes (SCG10 and transin) in PC12 cells; normal alpha(1)M, in contrast, produced little or no effect, This study demonstrates that alpha(1)M, the constitutive form of ar-macroglobulin in the rat, possesses the ability to promote NGF-mediated differentiation in PC12 cells, possibly via its direct action on TrkA receptors and TrkA-mediated signal transduction and gene expression.

alpha-2-macroglobulin receptor; alpha-macroglobulins; alpha(2)-macroglobulin; Biochemistry & Molecular Biology; caudate putamen; cerebral cortical-neurons; choline-acetyltransferase; delayed-response genes; immediate-early genes; myelin-associated glycoprotein; nerve growth factor receptor; neurite-promoting factor; Neurosciences & Neurology; ngf receptor; protein; signal; signal-transduction; transduction

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