Lysyl hydroxylase 2 is a specific telopeptide hydroxylase, while all three isoenzymes hydroxylate collagenous sequences

Takaluoma, Kati; Lantto, Juha; Myllyharju, Johanna

doi:10.1016/j.matbio.2007.01.002

Cited by 68 publications

(69 citation statements)

References 48 publications

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“…In addition, the levels of free and total Hyl residues in the purified type I collagen were essentially unchanged among the Sh clones and controls, suggesting that the LH activity of LH3, if any, is minimal for bone type I collagen. In the past years, several groups have tried to determine the sequence or collagen type specificity for the activities of LH isoforms (28,29,(63)(64)(65)(66)(67)(68)(69)(70). The results from these studies indicated that there are no strict collagen types or sequence requirements for the individual LH isoforms.…”

Section: Discussionmentioning

confidence: 99%

“…It was suggested that LH2b, the major isoform of LH2 in bone, mainly hydroxylates Lys residues in the telopeptide regions, thus determining the collagen crosslinking pathway (65,67,(71)(72)(73). In contrast, LH1 preferentially catalyzes the hydroxylation of Lys residues in the triple helical region of fibrillar collagen, including those residues pairing with the telopeptidyl Hyl/Lys aldehydes to form the intermolecular cross-links (29,65,66,68,74). As for LH3, its contribution to Lys hydroxylation in the helical region of fibrillar collagen is still unclear (28,29,65).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, LH1 preferentially catalyzes the hydroxylation of Lys residues in the triple helical region of fibrillar collagen, including those residues pairing with the telopeptidyl Hyl/Lys aldehydes to form the intermolecular cross-links (29,65,66,68,74). As for LH3, its contribution to Lys hydroxylation in the helical region of fibrillar collagen is still unclear (28,29,65). When the function of one isoform is impaired, compensatory mechanisms from the other two isoforms may occur and may depend largely on the tissue-specific expression of each isoform (70).…”

Section: Discussionmentioning

confidence: 99%

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Lysyl Hydroxylase 3 Glucosylates Galactosylhydroxylysine Residues in Type I Collagen in Osteoblast Culture

Sricholpech

Perdivara

Nagaoka

et al. 2011

Journal of Biological Chemistry

105

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Lysyl hydroxylase 3 (LH3), encoded by Plod3, is the multifunctional collagen-modifying enzyme possessing LH, hydroxylysine galactosyltransferase (GT), and galactosylhydroxylysine-glucosyltransferase (GGT) activities. Although an alteration in type I collagen glycosylation has been implicated in several osteogenic disorders, the role of LH3 in bone physiology has never been investigated. To elucidate the function of LH3 in bone type I collagen modifications, we used a short hairpin RNA technology in a mouse osteoblastic cell line, MC3T3-E1; generated single cell-derived clones stably suppressing LH3 (short hairpin (Sh) clones); and characterized the phenotype. Plod3 expression and the LH3 protein levels in the Sh clones were significantly suppressed when compared with the controls, MC3T3-E1, and the clone transfected with an empty vector. In comparison with controls, type I collagen synthesized by Sh clones (Sh collagen) showed a significant decrease in the extent of glucosylgalactosylhydroxylysine with a concomitant increase of galactosylhydroxylysine, whereas the total number of hydroxylysine residues was essentially unchanged. In an in vitro fibrillogenesis assay, Sh collagen showed accelerated fibrillogenesis compared with the controls. In addition, when recombinant LH3-V5/His protein was generated in 293 cells and subjected to GGT/GT activity assay, it showed GGT but not GT activity against denatured type I collagen. The results from this study clearly indicate that the major function of LH3 in osteoblasts is to glucosylate galactosylhydroxylysine residues in type I collagen and that an impairment of this LH3 function significantly affects type I collagen fibrillogenesis.Collagens are a large family of extracellular matrix proteins comprising at least 29 different genetic types (1, 2). Among those types, fibrillar type I collagen is the most abundant protein, and it is the major structural component in most connective tissues, including bone. One of the critical steps in collagen biosynthesis, which contributes to the functional integrity of the tissues, is the post-translational modifications, including the hydroxylation of specific proline (Pro) and lysine (Lys) residues, glycosylation of specific hydroxylysine (Hyl) 2 residues, and the formation of covalent intermolecular cross-links. Although several functions have been proposed for collagen glycosylation, such as control of collagen fibrillogenesis (3-7), cross-linking (8 -14), remodeling (15)(16)(17)(18)(19)(20)(21)(22), and collagen-cell interaction (23, 24), the function is still not well defined due in part to the lack of clear understanding in the mechanism of this modification.In fibrillar collagens, glycosylation occurs at specific Hyl residues by hydroxylysine galactosyltransferase (GT) (EC 2.4.1.50) and galactosylhydroxylysine-glucosyltransferase (GGT) (EC 2.4.1.66) resulting in the formation of galactosylhydroxylysine (G-Hyl) and glucosylgalactosylhydroxylysine (GGHyl), respectively. Recently, these enzymatic activities were found in the multi...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lysyl Hydroxylase 3 Glucosylates Galactosylhydroxylysine Residues in Type I Collagen in Osteoblast Culture

Sricholpech

Perdivara

Nagaoka

et al. 2011

Journal of Biological Chemistry

105

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“…184 Endogenous collagen cross-links are mediated by both non-enzymatic and enzymatic reactions. Non-enzymatic collagen cross-links are mediated by oxidation and glycation processes, 185 while enzymatic reactions happen between the telopeptide and adjacent triple helical chains, 186 which is mediated by chemical reactions through lysyl oxidase covalent bonding. 187,188 This results in the formation of inter and intra-molecular and inter-microfibrillar cross-links.…”

Section: Cross-linkersmentioning

confidence: 99%

Bonding efficiency and durability: current possibilities

et al. 2017

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Bonding plays a major role in dentistry nowadays. Dental adhesives are used in association with composites to solve many restorative issues. However, the wide variety of bonding agents currently available makes it difficult for clinicians to choose the best alternative in terms of material and technique, especially when different clinical situations are considered. Moreover, although bonding agents allow for a more conservative restorative approach, achieving a durable adhesive interface remains a matter of concern, and this mainly due to degradation of the bonding complex in the challenging oral environment. This review aims to present strategies that are being used or those still in development which may help to prevent degradation. It is fundamental that professionals are aware of these strategies to counteract degradation as much as possible. None of them are efficient to completely solve this problem, but they certainly represent reasonable alternatives to increase the lifetime of adhesive restorations.

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“…Mediating these changes are lysyl hydroxylases (LH1, LH2, and LH3) encoded by distinct procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) genes; these intracellular enzymes induce hydroxylation of Lys residues on collagen prior to the formation of triple helical pro-collagen molecules (6)(7)(8)(9)(10)(11). Following secretion of pro-collagen molecules into the extracellular space, the telopeptidyl Hyl residues undergo LOX-induced oxidative deamination into Hyl ald , which then forms Hyl ald -derived aldimine cross-links Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells.…”

Section: Introductionmentioning

confidence: 99%