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- Title
Plumbagin promotes the generation of astrocytes from rat spinal cord neural progenitors via activation of the transcription factor Stat3.
- Authors
Yongquan Luo; Mughal, Mohamed R.; Tae-Gen Son Xin Ouyang; Haiyang Jiang; Weiming Luo; Qian-Sheng Yu; Greig, Nigel H.; Mattson, Mark P.
- 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 antiatherosclerotic, 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 bromodeoxyuridine. 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.
- Subjects
ASTROCYTES; SPINAL cord; NAPHTHOQUINONE; ANTINEOPLASTIC agents; CELL-mediated cytotoxicity; ANTIBODY-dependent cell cytotoxicity; PLUMBAGINALES; PLUMBAGINACEAE
- Publication
Journal of Neurochemistry, 2010, Vol 115, Issue 6, p1337
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2010.06780.x