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Hyperactivation of human acidic chitinase (Chia) for potential medical use

K. Okawa, M. Kijima, M. Ishii, N. Maeda, Y. Yasumura, M. Sakaguchi, M. Kimura, M. Uehara, E. Tabata, PO. Bauer, F. Oyama

. 2025 ; 301 (1) : 108100. [pub] 20241218

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25010432

Accumulation of environmental chitin in the lungs can lead to pulmonary fibrosis, characterized by inflammatory infiltration and fibrosis in acidic chitinase (Chia)-deficient mice. Transgenic expression of Chia in these mice ameliorated the symptoms, indicating the potential of enzyme supplementation as a promising therapeutic strategy for related lung diseases. This study focuses on utilizing hyperactivated human Chia, which exhibits low activity. We achieved significant activation of human Chia by incorporating nine amino acids derived from the crab-eating monkey (Macaca fascicularis) Chia, known for its robust chitin-degrading activity. The modified human Chia retained high activity across a broad pH spectrum and exhibited enhanced thermal stability. The amino acid substitutions associated with hyperactivation of human Chia activity occurred species specifically in monkey Chia. This discovery highlights the potential of hyperactivated Chia in treating pulmonary diseases resulting from chitin accumulation in human lungs.

Citace poskytuje Crossref.org

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$a Okawa, Kazuaki $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan
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$a Accumulation of environmental chitin in the lungs can lead to pulmonary fibrosis, characterized by inflammatory infiltration and fibrosis in acidic chitinase (Chia)-deficient mice. Transgenic expression of Chia in these mice ameliorated the symptoms, indicating the potential of enzyme supplementation as a promising therapeutic strategy for related lung diseases. This study focuses on utilizing hyperactivated human Chia, which exhibits low activity. We achieved significant activation of human Chia by incorporating nine amino acids derived from the crab-eating monkey (Macaca fascicularis) Chia, known for its robust chitin-degrading activity. The modified human Chia retained high activity across a broad pH spectrum and exhibited enhanced thermal stability. The amino acid substitutions associated with hyperactivation of human Chia activity occurred species specifically in monkey Chia. This discovery highlights the potential of hyperactivated Chia in treating pulmonary diseases resulting from chitin accumulation in human lungs.
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$a Kijima, Masashi $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan
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$a Ishii, Mana $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan
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$a Maeda, Nanako $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan
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$a Yasumura, Yudai $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan
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$a Sakaguchi, Masayoshi $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan
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$a Kimura, Masahiro $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan; School of Bioscience and Biotechnology, Tokyo University of Technology, Hachioji, Tokyo, Japan
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$a Uehara, Maiko $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan
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$a Tabata, Eri $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan; Japan Society for the Promotion of Science (PD), Tokyo, Japan
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$a Bauer, Peter O $u Bioinova a.s., Prague, Czech Republic
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$a Oyama, Fumitaka $u Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo, Japan. Electronic address: f-oyama@cc.kogakuin.ac.jp
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