Puma, but not noxa is essential for oligodendroglial cell death.
The mechanisms involved in oligodendroglial cell death in human demyelinating diseases are only partly understood. Here, we demonstrate that the BH3 only protein Puma, but not Noxa, is essential for oligodendroglial cell death in toxic demyelination induced by the copper chelator cuprizone. Primary oligodendrocytes derived from Noxa- or Puma-deficient mice showed comparable differentiation to wild-type cells, but Puma-deficient oligodendrocytes were less susceptible to spontaneous, staurosporine, or nitric oxide-induced cell death. Furthermore, Puma was expressed in oligodendrocytes in multiple sclerosis (MS) lesions and Puma mRNA levels were upregulated in primary human oligodendrocytes upon cell death induction by staurosporine. Our data demonstrate that Puma is pivotal for oligodendroglial cell death induced by different cell death stimuli and might play a role in oligodendroglial cell death in MS.
Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
Karin
K
Hagemeier
Alexander
A
Lürbke
Stephanie
S
Hucke
Stefanie
S
Albrecht
Anna
A
Preisner
Elena
E
Klassen
Elke
E
Hoffmann
Qiao-Ling
QL
Cui
Jack
J
Antel J
Wolfgang
W
Brück
Luisca
L
Klotz
Tanja
T
Kuhlmann
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000378:metabolism*; D001921:Brain / Q000166:cytology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D008070:Lipopolysaccharides; C488588:PUMA protein, mouse; D010446:Peptide Fragments; C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; C069261:interferon gamma (1-39); D003471:Cuprizone; D007371:Interferon-gamma
BH3 only protein; apoptosis; cuprizone model; demyelinating diseases