TRPC channel-mediated neuroprotection by PDGF involves Pyk2/ERK/CREB pathway

H. Yao, F. Peng, Y. Fan, X. Zhu, G. Hu, Shilpa J Buch

Research output: Contribution to journalArticle

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Abstract

Platelet-derived growth factor-BB (PDGF) has been reported to provide tropic support for neurons in the central nervous system. The protective role of PDGF on dopaminergic neurons, especially in the context of HIV-associated dementia (HAD), however, remains largely unknown. Here, we show that exogenous PDGF was neuroprotective against toxicity induced by HIV-1 Tat in primary midbrain neurons. Furthermore, we report the involvement of transient receptor potential canonical (TRPC) channels in PDGF-mediated neuroprotection. TRPC channels are Ca2+ -permeable, nonselective cation channels with a variety of physiological functions. Blocking TRPC channels with either a blocker or short-interfering RNAs (specific for TRPC 5 and 6) in primary neurons resulted in suppression of both PDGF-mediated neuroprotection as well as elevations in intracellular Ca2+. PDGF-mediated neuroprotection involved parallel but distinct ERK/CREB and PI3K/Akt pathways. TRPC channel blocking also resulted in suppression of PDGF-induced Pyk2/ERK/CREB activation, but not Akt activation. Relevance of these findings in vivo was further corroborated by intrastriatal injections of PDGF and HIV-1 Tat in mice. Administration of PDGF was able to rescue the dopaminergic neurons in the substantia nigra from Tat-induced neurotoxicity. This effect was attenuated by pre-treatment of mice with the TRP blocker, thus underscoring the novel role of TRPC channels in the neuroprotection mediated by PDGF.

Original languageEnglish (US)
Pages (from-to)1681-1693
Number of pages13
JournalCell Death and Differentiation
Volume16
Issue number12
DOIs
StatePublished - Aug 17 2009

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Transient Receptor Potential Channels
MAP Kinase Signaling System
Dopaminergic Neurons
Neurons
HIV-1
platelet-derived growth factor BB
Neuroprotection
AIDS Dementia Complex
Substantia Nigra
Mesencephalon
Phosphatidylinositol 3-Kinases
Small Interfering RNA
Cations
Central Nervous System

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

TRPC channel-mediated neuroprotection by PDGF involves Pyk2/ERK/CREB pathway. / Yao, H.; Peng, F.; Fan, Y.; Zhu, X.; Hu, G.; Buch, Shilpa J.

In: Cell Death and Differentiation, Vol. 16, No. 12, 17.08.2009, p. 1681-1693.

Research output: Contribution to journalArticle

Yao, H. ; Peng, F. ; Fan, Y. ; Zhu, X. ; Hu, G. ; Buch, Shilpa J. / TRPC channel-mediated neuroprotection by PDGF involves Pyk2/ERK/CREB pathway. In: Cell Death and Differentiation. 2009 ; Vol. 16, No. 12. pp. 1681-1693.
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