Abstract
Fasting is accompanied by a decrease in collagen biosynthesis. The mechanism of this phenomenon involves inhibition of prolidase activity, an enzyme that plays a key role in upregulation of collagen metabolism. The mechanism of fasting-induced inhibition of prolidase activity is not known. Phosphoenolpyruvate (PEP) is known as a strong inhibitor of prolidase activity. It exerts this effect by inhibition of the enzyme phosphorylation. Unphosphorylated prolidase is inactive. One may expect that fasting-associated increase in posphoenolpyruvate content in animal tissues may be a factor which inactivates prolidase and makes it inactive in collagen biosynthesis. We measured the levels of phosphoenolpyruvate, pyruvate, and pyruvate kinase in the skin of control and fasted rats and correlated these parameters with prolidase expression, prolidase activity and collagen biosynthesis in this tissue. Significant increase of PEP concentration (about 30%) was found in the skin of fasted rats. In the same time prolidase activity and collagen biosynthesis decreased by about 50% and 30%, respectively, compared to controls. It is known that phosphoenolpyruvate is converted to pyruvate by the action of pyruvate kinase. Since fasting significantly decreases the activity of this enzyme, one may suggest that the accumulation of PEP is caused by a reduced utilisation of this metabolite. As demonstrated by Western immunoblot analysis the decrease in prolidase activity was not accompanied by a decrease in the amount of the enzyme protein. Instead, a decrease in the enzyme phosphorylation was observed. The reduction in phosphorylation seems to be responsible for the decrease in prolidase activity. These data suggest that fasting-evoked accumulation of PEP reduces the activity of prolidase, providing a mechanism for inhibition of collagen biosynthesis in the skin. (Mol Cell Biochem 265: 203–208, 2004)
Similar content being viewed by others
References
Cechowska-Pasko M, Palka J: Inhibition of collagen biosynthesis and increases in low molecular weight IGF-I binding proteins in the skin of fasted rats. Comp Biochem Physiol 127C: 49–59, 2000
Myara I, Charpentier C, Lemonnier A: Prolidase and prolidase defi-ciency. Life Sci 34: 1985–1998, 1984
Mock WL, Green PC, Boyer KD: Specificity and pH dependence for acrylproline cleavage by prolidase. J Biol Chem 265: 1960–1965, 1990
Chamson A, Voigtlander V, Myara I, Frey J: Collagen biosynthetic anomalies in prolidase deficiency: Effect of glycyl-L-proline on the degradation of newly synthesized collagen. Clin Physiol Biochem 7: 128–136, 1989
Yaron A, Naider F: Proline-dependent structural and biological prop-erties of peptides and proteins. Crit Rev Biochem Mol Biol 28: 31–81, 1993
Jackson SH, Dennis AW, Greenberg M: Iminodipeptiduria: A genetic defect in recycling collagen; a method for determining prolidase in ery-throcytes. CMA J 113: 759–763, 1975
Goodman SI, Solomons CC, Muscheinhein F: A syndrome resembling lathyrism associated with iminodipeptiduria. Am J Med 45: 152–159, 1968
Myara I, Miech G, Fabre M, Mangeot M, Lemonnier A: Changes in prolinase and prolidase activity during CCL4 administration inducing liver cytosolic and fibrosis in rat. Br J Exp Path 68: 7–13, 1987
Miltyk W, Karna E, Palka J: Inhibition of prolidase activity by non-steroid antiinflamatory drugs in cultured human skin fibroblasts. Pol J Pharmacol 48: 609–613, 1996
Palka JA, Miltyk W, Karna E, Wolczy` nski S: Modulation of prolidase activity during in vitro aging of human skin fibroblasts the role of extracellular matrix collagen. Tokai J Exp Clin Med 21: 207–213, 1996
Palka J, Karna E, Miltyk W: Fibroblast chemotaxis and prolidase activity modulation by insulin-like growth factor II and mannose 6-phosphate. Mol Cell Biochem 168: 177–183, 1997
Palka J, Phang JM: Prolidase activity in fibroblasts is regulated by interaction of extracellular matrix with cell surface integrin receptors. J Cell Biochem 67: 166–175, 1997
Palka JA, Phang JM: Prolidase in human breast cancer MCF-7 cells. Cancer Lett 127: 63–70, 1998
Senior B, Sadeghi-Nejad A: Hypoglycemia: a pathophysiologic approach. Acta Pediatr Scand 352: 1–27, 1989
Cechowska-Pasko M, Palka J: Age-dependent changes in glycoasmino-glycan content in the skin of fasted rats. A possible mechanism. Exp Toxic Pathol 52: 127–131, 2000
Radzicka A, Wolfenden R: Analogues of intermediates in the action of pig kidney prolidase. Biochemistry 30: 4160–4164, 1991
Groen AK, Vervoorn RC, Van der Meer R, Tager JM: Control of gluconeogenesis in rat liver cells. J Biol Chem 258: 14346–14353, 1983
Myara I, Charpentier C, Lemonnier A: Optimal conditions for prolidase assay by proline colorimetric determination: Application to imidodipeptiduria. Clin Chim Acta 125: 193–205, 1982
Chinard FP: Photometric estimation of proline and ornithine. J Biol Chem 199: 91–95, 1952
Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685, 1970
Segal S, Blair AE, Wyngaarden JB: An enzymatic spectrophotometric method for the determination of pyruvic acid in blood. J Lab Clin Med 48: 137–142, 1956
Czok R, Lamprecht W: Pyruvate, phosphoenolpyruvate and D-glycerate-2-phosphate. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Wiley-VCH Publishers, Weinheim, Germany, 1983, pp 1446–1451
Collins LB, Thomas TD: Pyruvate kinase of Streptococcus lactis. J Bacteriol 120: 52–58, 1974
Peterkofsky B, Chojkier M, Bateman J: Determination of collagen synthesis in tissue and cell culture system. In: H. Furthmayr (ed). Immuno-chemistry of the Extracellular Matrix. CRC Press, Boca Raton, Florida, USA,1982, pp 19–47
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976
Prockop DJ, Undenfriend S: A specific method for the analysis of hydroxyproline in tissues and urine. Anal Biochem 1: 228–239, 1960
Sura¿y` nski A, Palka J, Wolczy` nski S: Phosphorylation of prolidase increases the enzyme activity. Mol Cell Biochem 220: 95–101, 2001
Miltyk W, Palka JA: Potential role of pyrroline 5-carboxylate in regulation of collagen biosynthesis in cultured human skin fibroblasts. Comp Biochem Physiol 125(part A): 265–271, 2000
Karna E, Miltyk W, Wolczynski S, Palka JA: The potential mechanism for glutamine-induced collagen biosynthesis in cultured human skin fibroblasts. Comp Biochem Physiol B Biochem Mol Biol 130: 23–32, 2001
Galicka A, Wolczynski S, Anchim T, Surazynski A, Lesniewicz R, Palka J: Defects of type I procollagen metabolism correlated with decrease of prolidase activity in a case of lethal osteogenesis imperfecta. Eur J Biochem 268: 2172–2178, 2001
Muszyńska A, Palka J, Wolczyński S: Doxorubicin-induced inhibition of prolidase activity in human skin fibroblasts and its implication to impaired collagen biosynthesis. Pol J Pharmacol 50: 151–157, 1998
Karna E, Surazynski A, Palka: Collagen metabolism disturbances are accompanied by an increase in prolidase activity in lung carcinoma planoepitheliale. Int J Exp Pathol 81: 341–347, 2000
Saiki S, Yamaguchi K, Chijiiwa K, Shimizu S, Hamasaki N, Tanaka M: Phosphoenolpyruvate prevents the decline in hepatic ATP and energy charge after ischemia and reperfusion injury in rats. J Surg Res 73: 59–65, 1997
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cechowska-Pasko, M., Palka, J. & Bańkowski, E. Fasting-induced inhibition of collagen biosynthesis in rat skin. A possible role for phosphoenolpyruvate in this process. Mol Cell Biochem 265, 203–208 (2004). https://doi.org/10.1023/B:MCBI.0000044397.32748.23
Issue Date:
DOI: https://doi.org/10.1023/B:MCBI.0000044397.32748.23