Effects of Elastin Peptides on Ion Fluxes
The degradation of elastin by elastase-type enzymes was shown to play an important role in several pathological processes such as the development of emphysema (Crystal, 1976; Bignonet al., 1978), arteriosclerosis (Robertet al., 1980, 1984), and a variety of skin diseases (Franceset al., 1984). All these enzymes, although of different natures (Bourdillonet al., 1984), are able to hydrolyze elastin and release soluble peptides. The released peptides (mainly kappa elastin, KE) were shown to have a variety of biological properties (Robertet al., 1970; Jacobet al., 1984). One of these was the chemotactic effect on monocyte and fibroblasts (Senioret al., 1980). Robertet al. (1967, 1970) demonstrated their antigenic nature. Rabbits immunized with elastin peptides were shown to develop severe arteriosclerosis (Robertet al., 1971; Jacobet al., 1984) and also lesions of pulmonary arteries. Transmembrane cation fluxes (Na+ , K+ , Ca2+ ) were shown to play an important role in cell activity regulation (Scullyet al., 1984; Blausteinet al., 1984). The chemotactic peptide receptors were shown to be coupled to the phosphoinositide-specific phospholipase C through a guanine nucleotide regulatory protein (Berridgeet al., 1984). This receptor activation involves hydrolysis of phosphoinositides followed by generation of inositol trisphosphate and diacylglycerol. The inositol trisphosphate is believed to induce the release of Ca2+ from an intracellular storage and as a consequence the level of intracellular free Ca2+ is increased (Reynolds, 1985). Furthermore, the formation of inositol tetrakisphosphate from inositol trisphosphate seems to have ionophore effects (Trimbleet al., 1987). Our aims were to investigate the effects of elastin peptides on ion fluxes and to elucidate their mechanism of action at the cellular and intracellular levels.
KeywordsPertussis Toxin Arachidonic Acid Release Inositol Trisphosphate cGMP Production Cation Flux
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- Bignon, J., and Robert, L., 1978, La revue du Médecin 19:764–778.Google Scholar
- Bourdillon, M. C., Hornebeck, W., Soleilhac, J. M., and Robert, L., 1984, Biochem. Soc. Trans. 12: 876–887.Google Scholar
- Crystal, R. G., 1976, The Biochemical Basis of Pulmonary Function ,Marcel Dekker, New York.Google Scholar
- Irvine, R. F., 1982, Biochemistry 204:3–10.Google Scholar
- Robert, L., Stein, F., Pezess, M. P., and Poullain, N., 1967, Arch. Mal. Coeur 60:233–241.Google Scholar
- Robert, L., and Robert, A. M., 1980, in Frontiers of Matrix Biology: Biology and Pathology of Elastic Tissues ,Vol. 8 (A. M. Robert and L. Robert, eds.), Karger, Basel, pp. 130–173.Google Scholar
- Robert, L., Chaudiere, J., and Jacotot, B., 1984, in: Regression of Atherosclerotic Lesions: Experimental Studies and Observations in Humans (M. R. Malinow and V. H. Blaton, eds.), NATO ASI Series, Life Sciences, vol. 79, Plenum Press, New York, pp. 145–173.Google Scholar
- Varga, Zs., Jacobs, M. P., Robert, L., and Fülöp, T., Jr., 1988a, Proc. Natl. Acad. Sci. (in press).Google Scholar