ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury.
The neurotrophin receptor p75 is induced by various injuries to the nervous system, but its role after injury has remained unclear. Here, we report that p75 is required for the death of oligodendrocytes following spinal cord injury, and its action is mediated mainly by proNGF. Oligodendrocytes undergoing apoptosis expressed p75, and the absence of p75 resulted in a decrease in the number of apoptotic oligodendrocytes and increased survival of oligodendrocytes. ProNGF is likely responsible for activating p75 in vivo, since the proNGF from the injured spinal cord induced apoptosis among p75(+/+), but not among p75(-/-), oligodendrocytes in culture, and its action was blocked by proNGF-specific antibody. Together, these data suggest that the role of proNGF is to eliminate damaged cells by activating the apoptotic machinery of p75 after injury.
Beattie
Michael S
MS
Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
Harrington
Anthony W
AW
Lee
Ramee
R
Kim
Ju Young
JY
Boyce
Sheri L
SL
Longo
Frank M
FM
Bresnahan
Jacqueline C
JC
Hempstead
Barbara L
BL
Yoon
Sung Ok
SO
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D009836:Oligodendroglia / Q000378:metabolism*; D011498:Protein Precursors / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011930:Reaction Time / Q000502:physiology; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D011993:Recombinant Fusion Proteins; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology
D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011498:Protein Precursors; D011506:Proteins; C428743:Rb1cc1 protein, mouse; D020800:Receptor, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; C489226:pro-nerve growth factor, mouse; D020932:Nerve Growth Factor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases