Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis

Kyunghee Byun, Jaewoo Kim, Sang Yun Cho, Brian Hutchinson, Se Ran Yang, Kyung Sun Kang, Moonjae Cho, Kyukye Hwang, Makoto Michikawa, Young Wook Jeon, Young Ki Paik, Bonghee Lee

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Niemann-Pick disease type C (NPC) is a fatal autosomal recessive cholesterol disorder characterized by severe progressive neurodegeneration. To unveil the mechanism of neurodegeneration, proteomic and morphological approaches were applied to the hippocampus in NPC -/- mouse. Two-DE was utilized to resolve the hippocampal protein expression profiles of 4- and 8-week-old NPC +/+ and -/- mice. Differentially expressed protein spots were identified by MALDI-TOF MS and database searching. At 4 weeks of age, there was no significant difference in protein profiles between NPC +/+ and -/- mice. However, at the age of 8 weeks, NPC +/+ and -/- mice showed marked difference in protein expressions. Among these, glutamate receptor 2 precursor was identified. The immunohistochemical study on neurotransporters showed that glial GABA transporter (GAT-3) increased in both 4- and 8-week-old NPC -/-mouse and glutamic acid decarboxylase (GAD-6) increased in 8-week-old NPC -/- mouse. Glial glutamate transporter, excitatory amino acids carrier-1 (EAAC1), decreased in 8-week-old NPC -/- mouse. In conclusion, our data may provide insight into the understanding of the basic mechanism through perturbation of protein networks and neurotransporter systems in a single gene knockout model of NPC disease.

Original languageEnglish
Pages (from-to)1230-1236
Number of pages7
JournalProteomics
Volume6
Issue number4
DOIs
Publication statusPublished - 2006 Feb 1

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Type C Niemann-Pick Disease
GABA Plasma Membrane Transport Proteins
Amino Acid Transport System X-AG
Proteomics
Hippocampus
Proteins
Neuroglia
Excitatory Amino Acids
Glutamate Decarboxylase
Glutamate Receptors
Gene Knockout Techniques
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Genes
Cholesterol
Databases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Byun, Kyunghee ; Kim, Jaewoo ; Cho, Sang Yun ; Hutchinson, Brian ; Yang, Se Ran ; Kang, Kyung Sun ; Cho, Moonjae ; Hwang, Kyukye ; Michikawa, Makoto ; Jeon, Young Wook ; Paik, Young Ki ; Lee, Bonghee. / Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis. In: Proteomics. 2006 ; Vol. 6, No. 4. pp. 1230-1236.
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abstract = "Niemann-Pick disease type C (NPC) is a fatal autosomal recessive cholesterol disorder characterized by severe progressive neurodegeneration. To unveil the mechanism of neurodegeneration, proteomic and morphological approaches were applied to the hippocampus in NPC -/- mouse. Two-DE was utilized to resolve the hippocampal protein expression profiles of 4- and 8-week-old NPC +/+ and -/- mice. Differentially expressed protein spots were identified by MALDI-TOF MS and database searching. At 4 weeks of age, there was no significant difference in protein profiles between NPC +/+ and -/- mice. However, at the age of 8 weeks, NPC +/+ and -/- mice showed marked difference in protein expressions. Among these, glutamate receptor 2 precursor was identified. The immunohistochemical study on neurotransporters showed that glial GABA transporter (GAT-3) increased in both 4- and 8-week-old NPC -/-mouse and glutamic acid decarboxylase (GAD-6) increased in 8-week-old NPC -/- mouse. Glial glutamate transporter, excitatory amino acids carrier-1 (EAAC1), decreased in 8-week-old NPC -/- mouse. In conclusion, our data may provide insight into the understanding of the basic mechanism through perturbation of protein networks and neurotransporter systems in a single gene knockout model of NPC disease.",
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Byun, K, Kim, J, Cho, SY, Hutchinson, B, Yang, SR, Kang, KS, Cho, M, Hwang, K, Michikawa, M, Jeon, YW, Paik, YK & Lee, B 2006, 'Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis', Proteomics, vol. 6, no. 4, pp. 1230-1236. https://doi.org/10.1002/pmic.200500412

Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis. / Byun, Kyunghee; Kim, Jaewoo; Cho, Sang Yun; Hutchinson, Brian; Yang, Se Ran; Kang, Kyung Sun; Cho, Moonjae; Hwang, Kyukye; Michikawa, Makoto; Jeon, Young Wook; Paik, Young Ki; Lee, Bonghee.

In: Proteomics, Vol. 6, No. 4, 01.02.2006, p. 1230-1236.

Research output: Contribution to journalArticle

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AU - Kim, Jaewoo

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AU - Hutchinson, Brian

AU - Yang, Se Ran

AU - Kang, Kyung Sun

AU - Cho, Moonjae

AU - Hwang, Kyukye

AU - Michikawa, Makoto

AU - Jeon, Young Wook

AU - Paik, Young Ki

AU - Lee, Bonghee

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N2 - Niemann-Pick disease type C (NPC) is a fatal autosomal recessive cholesterol disorder characterized by severe progressive neurodegeneration. To unveil the mechanism of neurodegeneration, proteomic and morphological approaches were applied to the hippocampus in NPC -/- mouse. Two-DE was utilized to resolve the hippocampal protein expression profiles of 4- and 8-week-old NPC +/+ and -/- mice. Differentially expressed protein spots were identified by MALDI-TOF MS and database searching. At 4 weeks of age, there was no significant difference in protein profiles between NPC +/+ and -/- mice. However, at the age of 8 weeks, NPC +/+ and -/- mice showed marked difference in protein expressions. Among these, glutamate receptor 2 precursor was identified. The immunohistochemical study on neurotransporters showed that glial GABA transporter (GAT-3) increased in both 4- and 8-week-old NPC -/-mouse and glutamic acid decarboxylase (GAD-6) increased in 8-week-old NPC -/- mouse. Glial glutamate transporter, excitatory amino acids carrier-1 (EAAC1), decreased in 8-week-old NPC -/- mouse. In conclusion, our data may provide insight into the understanding of the basic mechanism through perturbation of protein networks and neurotransporter systems in a single gene knockout model of NPC disease.

AB - Niemann-Pick disease type C (NPC) is a fatal autosomal recessive cholesterol disorder characterized by severe progressive neurodegeneration. To unveil the mechanism of neurodegeneration, proteomic and morphological approaches were applied to the hippocampus in NPC -/- mouse. Two-DE was utilized to resolve the hippocampal protein expression profiles of 4- and 8-week-old NPC +/+ and -/- mice. Differentially expressed protein spots were identified by MALDI-TOF MS and database searching. At 4 weeks of age, there was no significant difference in protein profiles between NPC +/+ and -/- mice. However, at the age of 8 weeks, NPC +/+ and -/- mice showed marked difference in protein expressions. Among these, glutamate receptor 2 precursor was identified. The immunohistochemical study on neurotransporters showed that glial GABA transporter (GAT-3) increased in both 4- and 8-week-old NPC -/-mouse and glutamic acid decarboxylase (GAD-6) increased in 8-week-old NPC -/- mouse. Glial glutamate transporter, excitatory amino acids carrier-1 (EAAC1), decreased in 8-week-old NPC -/- mouse. In conclusion, our data may provide insight into the understanding of the basic mechanism through perturbation of protein networks and neurotransporter systems in a single gene knockout model of NPC disease.

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