CELLULAR AND SUBCELLULAR COMPARTMENTATION OF CREATINE-KINASE IN BRAIN

被引:30
作者
MANOS, P
BRYAN, GK
机构
关键词
ASTROCYTE; BRAIN DEVELOPMENT; CONFOCAL MICROSCOPY; NEURON; NUCLEAR ENERGY METABOLISM; OLIGODENDROCYTE;
D O I
10.1159/000111344
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Creatine kinase (CK) catalyzes a reversible transphosphorylation reaction that is believed to play a crucial role in the maintenance and channeling of high energy phosphate in tissues with high energy demands. In rat brain development, cytosolic (nonmitochondrial) CK levels increase rapidly during the peak period of myelination and remain high in the adult. The cellular compartmentation of CK was investigated through the use of primary cultures of neurons, oligodendrocytes and astrocytes. The CK activity in cultured oligodendrocytes, which expressed both enzymatic and immunocytochemical markers of myelin, was the highest of the cell types examined and comparable to levels measured in whole adult brain; these observations suggest a role for CK in myelinogenesis. We found that low density, dividing astrocyte cultures also exhibited high B-CK (brain isoenzyme of CK) immunoreactivity, with the nuclear CK staining being especially intense. We studied these cultured astrocytes in more detail with respect to their intense nuclear CK immunoreactivity. Optical sections of astrocyte nuclei taken with a confocal microscope show that the high B-CK present is actually contained within the nucleus, with a nucleoplasmic distribution that does not co-localize with DNA or RNA. To ascertain whether the high nuclear B-CK in proliferating astrocytes correlated with ongoing cell division, we conducted experiments with confluent, nondividing cultures. These results show that both CK enzyme activity and immunoreactivity are high in the nucleus of proliferating astrocytes, and significantly reduced in the nucleus of quiescent, nondividing astrocytes. The high level of CK protein and activity in the nucleus of proliferating astrocytes suggests a role for CK in cell division/nuclear function. We detail a model for a nuclear creatine-P/CK energy shuttle in astrocytes, which we propose contributes substantially to astrocyte nuclear function and is likely present in oligodendrocytes as well.
引用
收藏
页码:271 / 279
页数:9
相关论文
共 14 条
[1]  
AGUTTER PS, 1991, NUCLEUS CYTOPLASM, P77
[2]   EXPRESSION OF A RAT-BRAIN CREATINE KINASE-BETA-GALACTOSIDASE FUSION PROTEIN IN ESCHERICHIA-COLI AND DERIVATION OF THE COMPLETE AMINO-ACID-SEQUENCE OF RAT-BRAIN CREATINE-KINASE [J].
BENFIELD, PA ;
HENDERSON, L ;
PEARSON, ML .
GENE, 1985, 39 (2-3) :263-267
[3]   TRANSPORT OF ENERGY IN MUSCLE - THE PHOSPHORYLCREATINE SHUTTLE [J].
BESSMAN, SP ;
GEIGER, PJ .
SCIENCE, 1981, 211 (4481) :448-452
[4]   THE CREATINE-CREATINE PHOSPHATE ENERGY SHUTTLE [J].
BESSMAN, SP ;
CARPENTER, CL .
ANNUAL REVIEW OF BIOCHEMISTRY, 1985, 54 :831-862
[5]   GROWTH REQUIREMENTS INVITRO OF OLIGODENDROCYTE CELL-LINES AND NEONATAL RAT-BRAIN OLIGODENDROCYTES [J].
BOTTENSTEIN, JE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (06) :1955-1959
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]   CREATINE-KINASE ROLE IN ANAPHASE CHROMOSOME MOVEMENT [J].
CANDE, WZ .
NATURE, 1983, 304 (5926) :557-558
[8]   PROTEIN IMPORT INTO THE CELL-NUCLEUS [J].
DINGWALL, C ;
LASKEY, RA .
ANNUAL REVIEW OF CELL BIOLOGY, 1986, 2 :367-390
[9]   MATURATIONAL INCREASE IN MOUSE-BRAIN CREATINE-KINASE REACTION-RATES SHOWN BY PHOSPHORUS MAGNETIC-RESONANCE [J].
HOLTZMAN, D ;
MCFARLAND, EW ;
JACOBS, D ;
OFFUTT, MC ;
NEURINGER, LJ .
DEVELOPMENTAL BRAIN RESEARCH, 1991, 58 (02) :181-188
[10]   CHANGES DURING DEVELOPMENT OF MOUSE BRAIN IN ACTIVITIES AND SUBCELLULAR DISTRIBUTIONS OF CREATINE AND ADENYLATE KINASES [J].
LAPIN, EP ;
MAKER, HS ;
LEHRER, GM .
JOURNAL OF NEUROCHEMISTRY, 1974, 23 (03) :465-469