コラーゲンのリシン残基水酸化 : 全身および口腔領域の結合組織の生理・病理学的性状決定に重要な翻訳後修飾

71 References
  • MATSUURA Takashi
    Section of Fixed Prosthodontics, Department of Oral Rehabilitation, Fukuoka Dental College
  • KATAFUCHI Michitsuna
    Section of Fixed Prosthodontics, Department of Oral Rehabilitation, Fukuoka Dental College
  • TOKUTOMI Kentaro
    Section of Fixed Prosthodontics, Department of Oral Rehabilitation, Fukuoka Dental College
  • SATO Hironobu
    Section of Fixed Prosthodontics, Department of Oral Rehabilitation, Fukuoka Dental College

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  • Lysine Hydroxylation of Collagen : an Important Posttranslational Modification for Physiological and Pathophysiological Conditions of General and Oral Connective Tissues

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Abstract

Among extensive posttranslational modifications of collagen, lysine (Lys) hydroxylation is important for physiological and pathophysiological conditions of connective tissues. This review describes molecular mechanism of Lys hydroxylation and its implications in physiological and pathophysiological conditions of connective tissues. Lys hydroxylation is important for glycosylation and cross-linking of collagen, determining mechanical properties of tissues. The specific Lys residues are catalyzed by three isoforms of lysyl hydroxylase (LH, known as PLOD : procollagen-lysine, 2-oxoglutarate 5-dioxygenase). LH1 catalyzes Lys hydroxylation in the triple helical domain, while an alternatively spliced form of LH2, LH2b, does this in the telopeptide domain. LH3 is a multifunctional enzyme, possessing activities of LH, hydroxylysyl galactosyl-transferase (GT), and galactosylhydroxylysyl glucosyltransferase (GGT). Three autosomal diseases related to lh (plod) genes or LH activities are well known. Ehlers-Danlos syndrome VIA is caused by mutations of lh1, clinically characterized by joint laxity, muscle hypotonia, and kyphoscoliosis. Bruck syndrome is caused by mutations of lh2, characterized by fragile bones and short stature. Rieger syndrome is characterized by dental hypoplasia, craniofacial dysmorphism, umbilical stump abnormalities, and some patients have mutations in pitx2 (a member of the bi-coid/paired-like homeobox transcription factor family), likely resulting in altered expression of lh1, a downstream target of pitx2. Other than autosomal diseases, fibrosis shows overhydroxylation of Lys residues within telopeptide domains by up-regulated expression of lh2b. Osteoporosis also exhibits overhydroxylation of Lys residues in skeletal bones including the mandible. In healthy oral mucosae, gingiva has a higher extent of Lys hydroxylation than alveolar mucosa. Lys hydroxylation, important for physiological and pathophysiological conditions of various tissues, may become a key posttranslational modification for determining individual differences in oral tissue stability and its age-dependent change.

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