Growth arrest and DNA damage protein 45b (Gadd45b) protects retinal ganglion cells from injuries.
We hypothesize that neurons have protective mechanisms against adverse local conditions that improve the chances of cell survival. In the present study, we find that growth arrest and DNA damage protein 45b (Gadd45b), a previously unknown molecule in neurons of any type, is neuroprotective in retinal ganglion cells (RGCs) in the retina. Gadd45b is upregulated in RGCs in response to oxidative stress, aging and elevated intraocular pressure. Using Gadd45b siRNA, we show that Gadd45b protects RGCs from dying against different neuronal injuries including oxidative stress, TNFalpha cytotoxicity, and glutamate excitotoxicity in vitro. Using Gadd45b knockout mice, we find that Gadd45b protects RGCs from dying against oxidative stress in vivo. Our data suggest that Gadd45b is an important component of the intrinsic neuroprotective mechanisms of RGC neurons in the retina and, perhaps in the CNS as well.
Liu
Bin
B
Department of Ophthalmology, Northwestern University School of Medicine, Chicago, IL 60611, USA. b-liu@northwestern.edu
Suyeoka
Genn
G
Papa
Salvatore
S
Franzoso
Guido
G
Neufeld
Arthur H
AH
D000375:Aging / Q000502:physiology; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000633:toxicity; D007429:Intraocular Pressure / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D010269:Paraquat / Q000633:toxicity; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D018698:Glutamic Acid; D010269:Paraquat; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C508094:Gadd45b protein, rat