Plumbagin promotes the generation of astrocytes from rat spinal cord neural progenitors via activation of the transcription factor Stat3

Yongquan Luo, Mohamed R. Mughal, Tae Gen Son Xin Ouyang, Haiyang Jiang, Weiming Luo, Qian Sheng Yu, Nigel H. Greig, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Plumbagin (5-hydroxy-2-methyl-1,4 naphthoquinone) is a naturally occurring low molecular weight lipophilic phytochemical derived from roots of plants of the Plumbago genus. Plumbagin has been reported to have several clinically relevant biological activities in non-neural cells, including anti-atherosclerotic, anticoagulant, anticarcinogenic, antitumor, and bactericidal effects. In a recent screen of a panel of botanical pesticides, we identified plumbagin as having neuroprotective activity. In this study, we determined if plumbagin could modify the developmental fate of rat E14.5 embryonic neural progenitor cells (NPC). Plumbagin exhibited no cytotoxicity when applied to cultured NPC at concentrations below 1 μM. At a concentration of 0.1 μM, plumbagin significantly enhanced the proliferation of NPC as indicated by a 17% increase in the percentage of cells incorporating bromo-deoxyuridine. Plumbagin at a concentration of 0.1 pM (but not 0.1 μM), stimulated the production of astrocytes as indicated by increased GFAP expression. Plumbagin selectively induced the proliferation and differentiation of glial progenitor cells without affecting the proliferation or differentiation of neuron-restricted progenitors. Plumbagin (0.1 pM) rapidly activated the transcription factor signal transducer and activator of transcription 3 (Stat3) in NPC, and a Stat3 inhibitor peptide prevented both plumbagin-induced astrocyte formation and proliferation. These findings demonstrate the ability of a low molecular weight naturally occurring phytochemical to control the fate of glial progenitor cells by a mechanism involving the Stat3 signaling pathway.

Original languageEnglish (US)
Pages (from-to)1337-1349
Number of pages13
JournalJournal of Neurochemistry
Volume115
Issue number6
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • ciliary neurotrophic factor
  • GFAP
  • neural progenitors
  • neurogenesis; Stat3

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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