ABUNDANCE OF PLATELET-DERIVED GROWTH-FACTORS (PDGFS), PDGF RECEPTORS AND ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES IN BRAIN DECLINE WITH AGE

Platelet-derived growth factors (PDGFs) specifically bind to PDGF rece ptors (PDGFRs), resulting in their activation via autophosphorylation and subsequent triggering of a cascade of phosphorylation events that include mitogen-activated protein (MAP) kinases. Most of our knowledge concerning MAP kinase activation comes from studies of cultured cells in vitro, and Little is known about their activation in vivo. In the present study, we determined PDGF and PDGFR levels and MAP kinase acti vities, including extracellular signal-regulated protein kinases (ERK) and c-Jun NH2-terminal protein kinases (JNK) or stress-activated prot ein kinases (SAPK) in brain of young and older mice. Both PDGF and PDG FR proteins were most abundant in protein extracts from brain (cerebra l cortex) among tissues of heart, liver, spleen, lung and kidney, as d etermined by Western blot analysis. PDGFR proteins in brain differed s ignificantly between young (1 or 8 weeks) and older (14 months) mice a nd PDGFR phosphorylation was seen in all age groups examined by a spec ific antibody against phosphotyrosine. The highest activity of ERK2 wa s also observed in brain tissues, and this activity declined with age, although ERK1 and ERK2 protein levels were not significantly altered during development and aging. Furthermore, the activity and amount of JNK/SAPK proteins were the most abundant in brain tissues and did not change with age. Thus, our findings demonstrate that the highest level s of PDGFs and PDGFRs existed in brain, and constitutive activation of MAP kinases declined with age, suggesting that signal pathways mediat ed by PDGF-MAP kinase cascades are important components in coordinatin g growth and differentiation of neurone and glial cells during develop ment and aging. (C) 1998 Elsevier Science B.V.