Expression of creatine kinase isoenzyme genes during postnatal development of rat brain cerebellum: evidence for transcriptional regulation.
Transcription and accumulation of brain-type creatine kinase (CKB) mRNA and its protein was examined during postnatal development of rat brain cerebellum, the brain region containing highest CKB mRNA in the adult. CKB protein was extremely low at day 1, increased about 10-fold until week 4 and remained constant until week 10. This time course was paralleled by cerebellar CKB mRNA, which was also extremely low at day 1 and increased 5-fold during the first 3 weeks and then remained constant. High levels of CKB protein were also detected in cultured primary cerebellar granular neurons. Nuclear run-on assays directly showed that CKB mRNA accumulation during postnatal cerebellar development was due to increased transcription. When compared with cerebrum and whole brain, cerebellar CKB mRNA accumulation during postnatal development was temporally delayed. Analysis of myocyte enhancer factor (MEF)-2 and Sp1, factors known to initiate or sustain CKB transcription in tissues other than brain, revealed that MEF-2 in cerebellum was low at week 1 but increased 3.5-fold by week 7, while Sp1 remained unchanged. The increase in CKB protein during cerebellar postnatal development was coincident with that of the ubiquitous mitochondrial CK protein and mRNA, indicating that a functional phosphocreatine energy shuttle probably exists for efficient ATP regeneration in the cerebellum. This should be beneficial for the many energy-demanding requirements during cerebellar development, as indicated by the observed temporal co-expression of CKB with myelin basic protein, which is involved in axon myelination by oligodendrocytes.
Shen
Wei
W
Department of Biological Sciences, University of Delaware, 117 Wolf Hall, Newark, DE 19716, U.S.A.
Willis
Dianna
D
Zhang
Yanping
Y
Schlattner
Uwe
U
Wallimann
Theo
T
Molloy
George R
GR
D000818:Animals; D000831:Animals, Newborn; D001671:Biochemistry / Q000379:methods; D002478:Cells, Cultured; D002531:Cerebellum / Q000201:enzymology* / Q000254:growth & development*; D003402:Creatine Kinase / Q000235:genetics* / Q000378:metabolism*; D052276:Creatine Kinase, BB Form; D052281:Creatine Kinase, Mitochondrial Form; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D008297:Male; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D009474:Neurons / Q000201:enzymology; D051381:Rats; D020318:Rats, Long-Evans; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D064326:MEF2 Transcription Factors; D004676:Myelin Basic Protein; D018006:Myogenic Regulatory Factors; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D003402:Creatine Kinase; D052276:Creatine Kinase, BB Form; D052281:Creatine Kinase, Mitochondrial Form; D012260:Ribonucleases