Induced expression of cathepsins and cystatin C in a murine model of demyelination

Jianmei Ma, Kenji Tanaka, Gen Yamada, Kazuhiro Ikenaka

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

While proteolytic enzymes are involved in the pathogenesis of multiple sclerosis (MS), the involvement of cathepsins has not been characterized in detail. To better understand the role of cathepsins, cDNA microarray analysis was used to study the brains of proteolipid protein transgenic (plptg /-) mice, an animal model that closely mimics the failure of remyelination in MS. Analysis revealed upregulated expression of cathepsins L, H and B and their inhibitor, cystatin C. By in situ hybridization, the induction of cathepsins was primarily limited to microglia/macrophages of the white matter, with continuous expression from 2 to 8 months of age. Elevated protein level of cathepsins was confirmed at 4 months of age. In contrast, elevated expression of cystatin C was found in astrocytes. The ratio of microglia/macrophages to astrocytes increased throughout the course of demyelination, suggesting that the ratio of secreted cathepsins to cystatin C increased during that period. We propose that in MS, remyelination may be impaired by increasing activity of cathepsins inadequately controlled by cystatin C.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalNeurochemical Research
Volume32
Issue number2
DOIs
Publication statusPublished - 2007 Feb
Externally publishedYes

Fingerprint

Cathepsin C
Cystatin C
Cathepsins
Demyelinating Diseases
Multiple Sclerosis
Macrophages
Microglia
Astrocytes
Cathepsin H
Proteolipids
Cathepsin L
Cathepsin B
Genetically Modified Animals
Microarray Analysis
Microarrays
Oligonucleotide Array Sequence Analysis
Transgenic Mice
In Situ Hybridization
Brain
Animals

Keywords

  • Brain
  • Cathepsin
  • Cystatin C
  • Demyelination
  • In situ hybridization

ASJC Scopus subject areas

  • Biochemistry
  • Neuroscience(all)

Cite this

Induced expression of cathepsins and cystatin C in a murine model of demyelination. / Ma, Jianmei; Tanaka, Kenji; Yamada, Gen; Ikenaka, Kazuhiro.

In: Neurochemical Research, Vol. 32, No. 2, 02.2007, p. 311-320.

Research output: Contribution to journalArticle

Ma, Jianmei ; Tanaka, Kenji ; Yamada, Gen ; Ikenaka, Kazuhiro. / Induced expression of cathepsins and cystatin C in a murine model of demyelination. In: Neurochemical Research. 2007 ; Vol. 32, No. 2. pp. 311-320.
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