RRC ID 19287
著者 Kinugawa M, Fukuzawa S, Tachibana K.
タイトル Skeletal protein protection: the mode of action of an anti-osteoporotic marine alkaloid, norzoanthamine.
ジャーナル J Bone Miner Metab
Abstract Bone is composed of mineralized collagen fibrils. A marine alkaloid, norzoanthamine, accelerates the formation of a collagen-hydroxyapatite composite and enhances collagen release from an immobilized matrix vesicle model. Norzoanthamine recognizes a peptide chain nonspecifically and stabilizes its secondary structure, and collagen has polyvalent binding sites for norzoanthamine. This collagen-norzoanthamine supramolecular association is considered to be one of the most significant modes of action for enhancement of bone formation. The facts that norzoanthamine is nontoxic and that it has a collagen protective activity indicate that it may provide significant therapeutic benefits. In particular, it may be a promising drug candidate for osteoporosis treatment and prevention. Interestingly, norzoanthamine suppressed the proteolysis of not only collagen but also elastin and bovine serum albumin, so it apparently has a universal protective effect of guarding extracellular matrix proteins from degradation. This result suggests that norzoanthamine protect skeletal proteins in the host animal body from external stresses and possibly enhance survival.
巻・号 27(3)
ページ 303-14
公開日 2009-1-1
DOI 10.1007/s00774-009-0049-7
PMID 19277454
MeSH Alkaline Phosphatase / metabolism Alkaloids / chemistry Alkaloids / pharmacology Alkaloids / therapeutic use Animals Azepines / chemistry Azepines / pharmacology* Azepines / therapeutic use* Bone and Bones / drug effects Bone and Bones / metabolism* Cell Shape / drug effects Cell Survival / drug effects Circular Dichroism Collagen / metabolism Durapatite / metabolism Fluorescein-5-isothiocyanate Heterocyclic Compounds, 4 or More Rings / chemistry Heterocyclic Compounds, 4 or More Rings / pharmacology Heterocyclic Compounds, 4 or More Rings / therapeutic use Matrix Metalloproteinase Inhibitors Mice Nephelometry and Turbidimetry Osteoporosis / drug therapy* Pancreatic Elastase / antagonists & inhibitors Protease Inhibitors / pharmacology Protein Processing, Post-Translational / drug effects Proteins / metabolism* Quinolines / chemistry Quinolines / pharmacology* Quinolines / therapeutic use* Spectrophotometry, Ultraviolet Trypsin / metabolism
IF 2.297
引用数 18
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL ENDOCRINOLOGY & METABOLISM
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)