Abstract

Collagen crosslinking will be characterized in tendon, bone, skin, cartilage and lungs of rats. Using newly developed HPLC techniques for separation and quantitation of reduced and of nonreducible crosslinks, we intend to study turnover of different crosslinks in vivo. Precursor-product relationships will be defined in different tissues containing different collagen types. We will specifically test the hypothesis that certain key crosslinks are markers of the ultimate metabolic fate of collagen-degradation or deposition as fibers. Maturation of difunctional crosslinks to tri- and tetrafunctional products will be closely examined to ascertain the role of nonreducible crosslinks in the maturation process. These studies should allow us to begin to understand aspects of collagen deposition in the extracellular matrix of the lung in normal animals, and should serve as the requisite data base to allow systematic study of aberrations in these processes secondary to pathophysiology and disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032690-02
Application #
3344107
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California Davis
Department
Type
Schools of Veterinary Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Gerriets, J E; Reiser, K M; Last, J A (1996) Lung collagen cross-links in rats with experimentally induced pulmonary fibrosis. Biochim Biophys Acta 1316:121-31
Armstrong, L C; Last, J A (1995) Rat lysyl hydroxylase: molecular cloning, mRNA distribution and expression in a baculovirus system. Biochim Biophys Acta 1264:93-102
Sun, W; Wu, R; Last, J A (1994) Coordinated expression of a 45 kD protein and ozone toxicity in a human bronchial epithelial cell line. Am J Respir Cell Mol Biol 10:673-82
Armstrong, L C; Watkins, K; Pinkerton, K E et al. (1994) Collagen mRNA content and distribution in the lungs of rats exposed to ozone. Am J Respir Cell Mol Biol 11:25-34
Gerriets, J E; Curwin, S L; Last, J A (1993) Tendon hypertrophy is associated with increased hydroxylation of nonhelical lysine residues at two specific cross-linking sites in type I collagen. J Biol Chem 268:25553-60
Chen, J; Armstrong, L C; Liu, S J et al. (1991) Silica increases cytosolic free calcium ion concentration of alveolar macrophages in vitro. Toxicol Appl Pharmacol 111:211-20
Buckingham, B; Reiser, K M (1990) Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus. J Clin Invest 86:1046-54
Last, J A; Gerriets, J E; Armstrong, L C et al. (1990) Hydroxylation of collagen by lungs of rats administered bleomycin. Am J Respir Cell Mol Biol 2:543-8
Last, J A; Armstrong, L G; Reiser, K M (1990) Biosynthesis of collagen crosslinks. Int J Biochem 22:559-64
Last, J A; King Jr, T E; Nerlich, A G et al. (1990) Collagen cross-linking in adult patients with acute and chronic fibrotic lung disease. Molecular markers for fibrotic collagen. Am Rev Respir Dis 141:307-13

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