Muscle creatine kinase isoenzyme expression in adult human brain.

Hamburg, Robert; Friedman, D. L.; Olson, Eric N.; G.S, THANGAMUTHU; Cortez, M.Dolores; Goodman, Carl B.; Puleo, Peter; Perryman, M. Benjamin

doi:10.1016/s0021-9258(19)39340-8

Cited by 35 publications

(7 citation statements)

References 37 publications

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“…It is also supported by high amounts of cytosolic or mitochondrial creatine kinase isoenzymes found in granular and pyramidal cell layers of the hippocampus during postnatal development of rats as well as by high levels of expression of the creatine transporter in the pyramidal cell layer of adult rat brains (20,21). In humans, there is even evidence of muscle-type creatine kinase in pyramidal cells of the hippocampus proper (22).…”

Section: Discussionmentioning

confidence: 96%

Localized proton MRS of the human hippocampus: Metabolite concentrations and relaxation times

Choi

Frahm

1999

Magn. Reson. Med.

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Absolute concentrations and proton relaxation times of major metabolites in the human hippocampus were determined with use of fully relaxed, short-echo time STEAM localization sequences at 2.0 T (20 normal adults). Mean metabolite concentrations were 7.6 ؎ 0.9 mM for total N-acetylaspartate (tNAA), 6.9 ؎ 0.8 mM for total creatine (tCr), 2.1 ؎ 0.3 mM for cholinecontaining compounds (Cho), and 6.2 ؎ 0.9 mM for myo-inositol (Ins). The observation of relatively low tNAA and high Cho and Ins levels compared with cortical gray and white matter corresponds to a lower neuronal density and higher glial density than in the neocortex, in agreement with histologic findings. The data do not support a lateralization of metabolites. T1 and T2 relaxation times were in the range of 1400-1730 and 140-330 msec, respectively, similar to those in other brain regions. Magn

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Section: Discussionmentioning

confidence: 96%

Localized proton MRS of the human hippocampus: Metabolite concentrations and relaxation times

Choi

Frahm

1999

Magn. Reson. Med.

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“…93,94 Myosin light chain, fast skeletal muscle (MYLPF, 5-fold, P = 3.68 × 10 −4 ), and myosin light chain-1 (MYL1, 3-fold, P = 1.54 × 10 −2 ) were more abundant in DG compared to CA regions in this study and are the known skeletal muscle motor proteins involved in calcium binding. Creatine kinase-M (CKM) is the creatine kinase isoform present in the muscles, which is related to calcium metabolism, 95 and was 6-fold more abundant in DG compared to CA1, CA3, and CA4 and 5-fold more abundant compared to CA2 (P = 3.48 × 10 −11 ) in this study. Figure 6 shows the representative MS/MS spectrum of the peptide (LGSSEVEQVQLVVDGVK) identified corresponding to CKM.…”

Section: Other Major Findings In Hippocampal Subfieldsmentioning

confidence: 59%

“…Creatine kinase (CK) is a key cytosolic enzyme found in skeletal muscle, cardiac muscle (CKM isotype), and the brain (CKB isotype), which undergoes periodic fluctuations in energy requirements . In addition, the expression of CKM is also reported in the brain . It catalyzes the reversible conversion of creatine to creatine phosphate (CrP) by transferring gamma phosphate from ATP and resynthesis of ATP from CrP during high energy requirements, thereby playing an important energy homeostatic role in these tissues .…”

Section: Resultsmentioning

confidence: 99%

“…99 In addition, the expression of CKM is also reported in the brain. 95 It catalyzes the reversible conversion of creatine to creatine phosphate (CrP) by transferring gamma phosphate from ATP and resynthesis of ATP from CrP during high energy requirements, thereby playing an important energy homeostatic role in these tissues. 99 In this study, it was found to be 6fold more abundant (P = 3.48 × 10 −11 ) in DG compared to CA1, CA3, and CA4 and 5-fold more abundant compared to CA2.…”

Section: Other Major Findings In Hippocampal Subfieldsmentioning

confidence: 99%

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Proteomic Analysis of Adult Human Hippocampal Subfields Demonstrates Regional Heterogeneity in the Protein Expression

et al. 2022

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Background: Distinct hippocampal subfields are known to get affected during aging, psychiatric disorders, and various neurological and neurodegenerative conditions. To understand the biological processes associated with each subfield, it is important to understand its heterogeneity at the molecular level. To address this lacuna, we investigated the proteomic analysis of hippocampal subfieldsthe cornu ammonis sectors (CA1, CA2, CA3, CA4) and dentate gyrus (DG) from healthy adult human cohorts. Findings: Microdissection of hippocampal subfields from archived formalin-fixed paraffin-embedded tissue sections followed by TMT-based multiplexed proteomic analysis resulted in the identification of 5,593 proteins. Out of these, 890 proteins were found to be differentially abundant among the subfields. Further bioinformatics analysis suggested proteins related to gene splicing, transportation, myelination, structural activity, and learning processes to be differentially abundant in DG, CA4, CA3, CA2, and CA1, respectively. A subset of proteins was selected for immunohistochemistry-based validation in an independent set of hippocampal samples. Conclusions: We believe that our findings will effectively pave the way for further analysis of the hippocampal subdivisions and provide awareness of its subfield-specific association to various neurofunctional anomalies in the future. The current mass spectrometry data is deposited and publicly made available through ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD029697.

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“…We have been using the cytoplasmic creatine kinase (ck) genes as a model system to study differential gene regulation (4). The muscle ck gene (ckm) is expressed most prominently in differentiated skeletal and cardiac muscle tissue (51), although there are reports of significant expression in some nonmuscle tissues (21,27). The brain ck gene (ckb) has wider tissue distribution and is expressed at differing levels in many tissues with the probable exception of liver (48).…”

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confidence: 99%

Brain and Muscle Creatine Kinase Genes Contain Common TA-Rich Recognition Protein-Binding Regulatory Elements

Horlick

Hobson

Patterson

et al. 1990

Molecular and Cellular Biology

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We have previously reported that the rat brain creatine kinase (ckb) gene promoter contains an AT-rich sequence that is a binding site for a protein called TARP (TA-rich recognition protein). This AT-rich segment is a positively acting regulatory element for the ckb promoter. A similar AT-rich DNA segment is found at the 3' end of the 5' muscle-specific enhancer of the rat muscle creatine kinase (ckm) gene and has been shown to be necessary for full muscle-specific enhancer activity. In this report, we show that TARP binds not only to the ckb promoter but also to the AT-rich segment at the 3' end of the muscle-specific ckm enhancer. A second, weaker TARP-binding site was identified in the ckm enhancer and lies at the 5' end of the minimal enhancer segment. TARP was found in both muscle cells (C2 and L6 myotubes) and nonmuscle (HeLa) cells and appeared to be indistinguishable from both sources, as judged by gel retardation and footprinting assays. The TARP-binding sites in the ckm enhancer and the ckb promoter were found to be functionally interchangeable. We propose that TARP is active in both muscle and nonmuscle cells and that it is one of many potential activators that may interact with muscle-specific regulators to determine the myogenic phenotype.

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Muscle creatine kinase isoenzyme expression in adult human brain.

Cited by 35 publications

References 37 publications

Localized proton MRS of the human hippocampus: Metabolite concentrations and relaxation times

Localized proton MRS of the human hippocampus: Metabolite concentrations and relaxation times

Proteomic Analysis of Adult Human Hippocampal Subfields Demonstrates Regional Heterogeneity in the Protein Expression

Brain and Muscle Creatine Kinase Genes Contain Common TA-Rich Recognition Protein-Binding Regulatory Elements

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