Biochemical Analysis of Elastic Fiber Formation with a Frameshift-Mutated Tropoelastin (fmTE) at the C-Terminus of Tropoelastin
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概要
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Elastic fibers play an important role in characteristic elastic properties of tissues such as skin, lungs, ligaments, and blood vessels. Many of the disorders related to elastic fibers are due to errors in assembly, yet the basic mechanisms of this process remain unclear. Cutis laxa, which is caused by an elastin gene mutation, includes a rare and heterogeneous group of the disorders characterized by lax, inelastic skin. To investigate whether elastic fiber assembly insufficiency is a possible factor in cutis laxa, we compared normal tropoelastin (nTE) and frameshift-mutated tropoelastin (fmTE) from a patient with autosomal dominant cutis laxa using an in vitro elastic fiber assembly model, in which purified recombinant tropoelastin was added to the culture medium. Assembly was evaluated by immunofluorescence staining, the quantitative analysis of cross-linked amino acids, and semi-quantitative analysis of matrix-associated tropoelastin. Immunofluorescence microscopy indicated an approximate 50% decrease in the deposition of fmTE in the extracelluar matrix, in contrast to that of nTE. The amount of cross-linked amino acids unique to mature insoluble elastin in the fmTE assembly was also decreased by approximately 20%. In addition, we clarified that the molecular interaction between fmTE and the amino-terminal domain of fibrillin-1 or full-length fibulin-5 was significantly decreased. Our results suggest that the defect of fmTE fiber assembly is due, at least in part, to decreased molecular interactions between tropoelastin and the microfibrillar components fibulin-5 and fibrillin.
- 公益社団法人日本薬学会の論文
- 2006-06-01
著者
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Sakamoto Yoshimitsu
星薬科大学 臨床化学
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Wachi Hiroshi
Faculty Of Technokogy Tokyo University Of Agriculture And Technology
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Wachi Hiroshi
Department Of Clinical Chemistry Hoshi University School Of Pharmacy And Pharmaceutical Sciences
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Wachi Hiroshi
Department Of Clinical Chemistry Hoshi College Of Pharmacy
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SATO Fumiaki
Department of Surgical Neurology Jichi Medical School
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Wachi Hiroshi
星薬科大学 臨床化学教室
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SEYAMA Yoshiyuki
Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences
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Seyama Yoshiyuki
Department Of Clinical Chemistry Hoshi College Of Pharmacy
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Starcher Barry
Department Of Biochemistry University Of Texas Health Center
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Sato Fumiaki
Department Of Computational Intelligence And Systems Science Tokyo Institute Of Technology
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Sato Fumiaki
Department of Clinical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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SEYAMA YOSHIYUKI
Department of Biochemistry, Tokyo College of Pharmacy
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