Expression of transcription factors CREB and c-Fos in the brains of terminal Creutzfeldt-Jakob disease cases.
Expression levels and localization of transcription factors cAMP response element binding protein (CREB(1) and CREB(2)) and c-Fos, as well as levels of up-stream mitogen-activated protein kinases/extracellular signal-regulated kinases (ERK-1 and ERK-2) and p38 kinase, were examined in the brains (frontal cortex) of eleven cases with Creutzfeldt-Jakob disease (CJD) and five age-matched controls. Preserved expression levels of ERK-1-P, ERK-2-P and p38-P were observed in CJD. However, significantly reduced levels, as revealed by gel electrophoresis and Western blotting, and reduced numbers of immunoreactive nuclei, as seen by immunohistochemistry, to CREB, CREB-P, c-Fos and c-Fos-P were found in CJD when compared with controls. These observations point to exhausted CREB and c-Fos brain responses, in spite of preserved up-stream signaling kinases, thus favoring cell death in terminal stages of CJD.
Rodríguez
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A
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain.
Ferrer
I
I
D000368:Aged; D000369:Aged, 80 and over; D050882:CREB-Binding Protein / Q000378:metabolism*; D016022:Case-Control Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011180:Postmortem Changes; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D050882:CREB-Binding Protein; D020928:Mitogen-Activated Protein Kinases