The direct and indirect effects of serofendic acid on neuroprotection.
Serofendic acid is a novel neuroprotective factor isolated from fetal calf serum. To elucidate the mechanisms how serofendic acid exerts neuroprotection, we examined its effects on glutamate-induced excito-toxicity in mouse cortical neurons. The effects of serofendic acid on inflammatory cytokine and neurotrophin production by glial cells were also examined to evaluate the indirect neuroprotection. Serofendic acid significantly and dose dependently increased survival of mouse cortical neurons after 10 muM N-methyl-D-asparate (NMDA) exposure. However, it did not affect production of inflammatory cytokines and neurotrophins by microglia as assessed by reverse transciption polymerase chain reaction (RT-PCR) for mRNA expression and ELISA for protein levels, though it suppressed tumor necrosis factor (TNF)-alpha production by astrocytes. Thus, serofendic acid works directly on neurons to protect against glutamate toxicity. Suppression of TNF-alpha production by astoryctes may also synergistically exert neuroprotective functions of serofendic acid. Serofendic acid may be of use for the future therapeutic strategy against ischemic and degenerative neurological disorders.
Doi
Yukiko
Y
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Liang
Jianfeng
J
Kuno
Reiko
R
Zang
Guiqin
G
Kawanokuchi
Jun
J
Yawata
Izumi
I
Takeuchi
Hideyuki
H
Mizuno
Tetsuya
T
Suzumura
Akio
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology*; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*
D016207:Cytokines; D004224:Diterpenes; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C452642:serofendic acid; D018698:Glutamic Acid; D016202:N-Methylaspartate