Astroglia-mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity.
Uric acid (UA) has been demonstrated to reduce damage to neurons elicited by oxidative stress. However, our studies utilizing cultures derived from embryonic rat spinal cord indicate that an astroglia-mediated mechanism is involved in the effects of UA to protect neurons from glutamate toxicity. The damage elicted by glutamate to neurons in a mixed culture of spinal cord cells can be reversed by UA. Furthermore, addition of UA after the termination of glutamate exposure suggests that UA plays an active role in mediating neuroprotection rather than purely binding peroxynitrite, as previously thought. Importantly, in pure neuron cultures from the same tissue, UA does not protect against glutamate toxicity. Addition of astroglia to the pure neuron cultures restores the ability of UA to protect the neurons from glutamate-induced toxicity. Our results also suggest that glia provide EAAT-1 and EAAT-2 glutamate transporters to protect neurons from glutamate, that functional EAATs may be necessary to mediate the effects of UA, and that treatment with UA results in upregulation of EAAT-1 protein. Taken together, our data strongly suggest that astroglia in mixed cultures are essential for mediating the effects of UA, revealing a novel mechanism by which UA, a naturally produced substance in the body, may act to protect neurons from damage during insults such as spinal cord injury.
Du
Yangzhou
Y
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.
Chen
Christopher P
CP
Tseng
Chia-Yi
CY
Eisenberg
Yuval
Y
Firestein
Bonnie L
BL
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018698:Glutamic Acid / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D013116:Spinal Cord / Q000166:cytology; D014527:Uric Acid / Q000378:metabolism*
D018696:Neuroprotective Agents; D009498:Neurotoxins; D014527:Uric Acid; D018698:Glutamic Acid