Impact of Carbamylation on Type I Collagen Conformational Structure and Its Ability to Activate Human Polymorphonuclear Neutrophils

Jaisson, Stéphane; Lorimier, Sandrine; Ricard‐Blum, Sylvie; Sockalingum, Ganesh D.; Delevallée-Forte, Céline; Kegelaer, Grégory; Manfait, Michel; Garnotel, Roselyne; Gillery, Philippe

doi:10.1016/j.chembiol.2005.11.005

Cited by 88 publications

(111 citation statements)

References 42 publications

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“…Indeed, using methylglyoxal as glycating agent, it has been demonstrated that arginine within the RGD collagen binding sites, preferentially reacts with this compound and consequently affect HT1080 cell adhesion and spreading (23). Concerning carbamylation, its minor impact on tumor cell migration is in agreement with the capacity of this modified collagen to retain its triple helical structure as recently demonstrated by our laboratory using Raman microspectroscopy (31).…”

Section: Discussionsupporting

confidence: 63%

Impact of carbamylation and glycation of collagen type I on migration of HT1080 human fibrosarcoma cells

et al. 2012

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Abstract. Collagen type I is an abundant component of the extracellular matrix and due to its longevity, constitutes a prominent target of non-enzymatic post-translational in vivo modifications such as carbamylation and glycation. These protein modifications involved in aging, renal diseases and diabetes, are linked to elevated cancer risk. In this in vitro study, we investigated the impact of carbamylated and glycated collagen type I on the migratory behavior of the highly invasive HT1080 human fibrosarcoma cells. The proliferation of HT1080 on modified collagens did not differ from that on native form. The glycated collagen delayed the cell adhesion time whereas the carbamylated one had no effect. The migration ability of HT1080 was studied by quantifying single cell speed using videomicroscopy. Glycation strongly inhibited mean cell speed by 47% whereas carbamylation moderately affected it by 12%. In addition, the influence of these collagen modifications on actin and vinculin organization was studied. On the glycated collagen, 63% of cells revealed a dramatic loss of actin stress fibers vs. 28% on the carbamylated one. In these cells, disorganized F-actin was accompanied with a disturbance of vinculin and both proteins were localized at the rim of the cells. Concerning the focal adhesion kinase (FAK) expression, glycated collagen only induced a significant inhibition. Whereas, both collagen modifications provoked a differential inhibition of FAK phosphorylation state by 25% for carbamylation and 60% for glycation. In conclusion, our data suggest that, in vivo, collagen glycation and carbamylation may affect tumor cell metastasis. This suggestion is supported by clinical studies reporting less aggressive tumors in diabetic or uremic patients. Consequently, the impact of such posttranslational modifications has to be taken into account in order to better understand the link between aging, diabetes or uremia and cancer progression.

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Section: Discussionsupporting

confidence: 63%

Impact of carbamylation and glycation of collagen type I on migration of HT1080 human fibrosarcoma cells

et al. 2012

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“…It has been shown that glycoxidation rate increased as a function of age in skin collagen of various mammalian species or cartilage collagen in humans, potentially contributing to age-related impairments (11,34,41). However, other biochemical reactions are involved in molecular aging, such as carbamylation, which is caused by the reaction of proteins with isocyanic acid (4,(42)(43)(44)(45). Isocyanic acid is mainly derived from urea dissociation but may also be generated from thiocyanate metabolism or brought by environment (15,19,23).…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that the modification of only four HCit residues per α-chain is sufficient to induce local destabilization, leading to a decrease of thermal stability, or fibrillogenesis impairment or alter sensitivity to proteolysis by matrix metalloproteinases (42,43). In addition, collagen carbamylation leads to functional damages, because carbamylated collagen is able to alter oxidative functions of inflammatory cells (42).…”

Section: Discussionmentioning

confidence: 99%

Protein carbamylation is a hallmark of aging

Gorisse

Piètrement

Vuiblet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Aging is a progressive process determined by genetic and acquired factors. Among the latter are the chemical reactions referred to as nonenzymatic posttranslational modifications (NEPTMs), such as glycoxidation, which are responsible for protein molecular aging. Carbamylation is a more recently described NEPTM that is caused by the nonenzymatic binding of isocyanate derived from urea dissociation or myeloperoxidase-mediated catabolism of thiocyanate to free amino groups of proteins. This modification is considered an adverse reaction, because it induces alterations of protein and cell properties. It has been shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes, but nothing is known to date about tissue protein carbamylation during aging. To address this issue, we evaluated homocitrulline rate, the most characteristic carbamylation-derived product (CDP), over time in skin of mammalian species with different life expectancies. Our results show that carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of carbamylated proteins. Because of their remarkably long half-life, matrix proteins, like type I collagen and elastin, are preferential targets. Interestingly, the accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. In addition, homocitrulline accumulates more intensely than carboxymethyl-lysine, one of the major advanced glycation end products, suggesting the prominent role of carbamylation over glycoxidation reactions in age-related tissue alterations. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species that may significantly contribute in the structural and functional tissue damages encountered during aging.

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“…A prior study of collagen carbamylation indicated that destabilization of the triple helix is a contributor to relative MMP activity. Carbamylation of 11 Lys residues in type I collagen leads to a decrease in triple-helix stability (ϳ2°C) (63). Although the Lys residues most susceptible to carbamylation are distant from the actual MMP cleavage site (63), carbamylation results in an increase in MMP-2 activity (64).…”

Section: Nomentioning

confidence: 99%

“…Carbamylation of 11 Lys residues in type I collagen leads to a decrease in triple-helix stability (ϳ2°C) (63). Although the Lys residues most susceptible to carbamylation are distant from the actual MMP cleavage site (63), carbamylation results in an increase in MMP-2 activity (64). Thus, destabilization of the triple helix increases MMP-2 activity, which is analogous to what was observed in the present study.…”

Section: Nomentioning

confidence: 99%

The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

Lauer

Bhowmick

Tokmina‐Roszyk

et al. 2014

Journal of Biological Chemistry

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Background:The role of charged clusters in modulating MMP hydrolysis of collagen is unknown. Results: Triple-helical peptides containing charged motifs were as good or better substrates than the parent (non-chargeclustered) peptide. Conclusion: MMP-2 and MMP-9 greatly favored the presence of charged residues. Significance: The lack of Gly-Asp-Lys clusters in native collagens may diminish potential MMP-2 and MMP-9 collagenolytic activity.

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Impact of Carbamylation on Type I Collagen Conformational Structure and Its Ability to Activate Human Polymorphonuclear Neutrophils

Cited by 88 publications

References 42 publications

Impact of carbamylation and glycation of collagen type I on migration of HT1080 human fibrosarcoma cells

Impact of carbamylation and glycation of collagen type I on migration of HT1080 human fibrosarcoma cells

Protein carbamylation is a hallmark of aging

The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

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