Neuroprotective effects of PDGF against oxidative stress and the signaling pathway involved

Lianshun Zheng, Yoko Ishii, Ayano Tokunaga, Takeru Hamashima, Jie Shen, Qing Li Zhao, Shin Ishizawa, Toshihiko Fujimori, Yo Ichi Nabeshima, Hisashi Mori, Takashi Kondo, Masakiyo Sasahara*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

The neuroprotective effects of platelet-derived growth factor (PDGF) and the major signaling pathways involved in these were examined using primary cultured mouse cortical neurons subjected to H2O2-induced oxidative stress. The specific function of the PDGF β-receptor (PDGFR-β) was examined by the selective deletion of the corresponding gene using the Cre-loxP system in vitro. In wild-type neurons, PDGF-BB enhanced the survival of these neurons and suppressed H2O2-induced caspase-3 activation. The prosurvival effect of PDGF-AA was less than that of PDGF-BB. PDGF-BB highly activated Akt, extracellular signal-regulated kinase (ERK), c-jun amino-terminal kinase (JNK) and p38. PDGF-AA activated these molecules at lesser extent than PDGF-BB. In particular, PDGF-AA induced activation of Akt was at very low level. The neuroprotective effects of PDGF-BB were antagonized by inhibitors of phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase kinase (MEK), JNK and p38. The PDGFR-β-depleted neurons showed increased vulnerability to oxidative stress, and less responsiveness to PDGF-BB-induced cytoprotection and signal activation, in which Akt activation was most strongly suppressed. After all, these results demonstrated the neuroprotective effects of PDGF and the signaling pathways involved against oxidative stress. The effects of PDGF-BB were more potent than those of PDGF-AA. This might be due to the activation and additive effects of two PDGFRs after PDGF-BB stimulation. Furthermore, the PI3-K/Akt pathway that was deduced to be preferentially activated by PDGFR-β may explain the potent effects of PDGF-BB.

Original languageEnglish
Pages (from-to)1273-1284
Number of pages12
JournalJournal of Neuroscience Research
Volume88
Issue number6
DOIs
StatePublished - 2010/05/01

Keywords

  • MAP kinase
  • Neuroprotection
  • Oxidative stress
  • PI3-K/Akt kinase
  • Platelet-derived growth factor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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