Abstract
Uptake of external glucose and production of lactate were measured in freshly-excised bovine articular cartilage under O2 concentrations ranging from 21% (air) to zero (N2-bubbled). Anoxia (O2 concentration < 1% in the gas phase) severely inhibited both glucose uptake and lactate production. The decrease in lactate formation correlated closely with the decrease in glucose uptake, in a mole ratio of 2:1. This reduction in the rate of glycolysis in anoxic conditions is seen as evidence of a negative Pasteur effect in bovine articular cartilage. Anoxia also suppressed glycolysis in articular cartilage from horse, pig and sheep. Inhibitors acting on the glycolytic pathway (2-deoxy-D-glucose, iodoacetamide or fluoride) strongly decreased aerobic lactate production and ATP concentration, consistent with the belief that articular cartilage obtains its principal supply of ATP from substrate-level phosphorylation in glycolysis. Azide or cyanide lowered the ATP concentration in aerobic cartilage to approximately the same extent as did anoxia but, because glycolysis (lactate production) was also inhibited by these treatments, the importance of any mitochondrial ATP production could not be assessed. A negative Pasteur effect would make chondrocytes particularly liable to suffer a shortage of energy under anoxic conditions. Incorporation of [35S]sulphate into proteoglycan was severely curtailed by treatments, such as anoxia, which decreased the intracellular concentration of ATP.
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- Baker M. S., Feigan J., Lowther D. A. The mechanism of chondrocyte hydrogen peroxide damage. Depletion of intracellular ATP due to suppression of glycolysis caused by oxidation of glyceraldehyde-3-phosphate dehydrogenase. J Rheumatol. 1989 Jan;16(1):7–14. [PubMed] [Google Scholar]
- Brighton C. T., Lane J. M., Koh J. K. In vitro rabbit articular cartilage organ model. II. 35S incorporation in various oxygen tensions. Arthritis Rheum. 1974 May-Jun;17(3):245–252. doi: 10.1002/art.1780170307. [DOI] [PubMed] [Google Scholar]
- DULBECCO R., FREEMAN G. Plaque production by the polyoma virus. Virology. 1959 Jul;8(3):396–397. doi: 10.1016/0042-6822(59)90043-1. [DOI] [PubMed] [Google Scholar]
- Darling T. N., Davis D. G., London R. E., Blum J. J. Carbon dioxide abolishes the reverse Pasteur effect in Leishmania major promastigotes. Mol Biochem Parasitol. 1989 Mar 1;33(2):191–202. doi: 10.1016/0166-6851(89)90033-9. [DOI] [PubMed] [Google Scholar]
- Elliott K. A., Baker Z. The effects of oxidation-reduction potential indicator dyes on the metabolism of tumour and normal tissues. Biochem J. 1935 Oct;29(10):2396–2404. doi: 10.1042/bj0292396. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HEYTLER P. G., PRICHARD W. W. A new class of uncoupling agents--carbonyl cyanide phenylhydrazones. Biochem Biophys Res Commun. 1962 May 4;7:272–275. doi: 10.1016/0006-291x(62)90189-4. [DOI] [PubMed] [Google Scholar]
- Hatefi Y. The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem. 1985;54:1015–1069. doi: 10.1146/annurev.bi.54.070185.005055. [DOI] [PubMed] [Google Scholar]
- Hills G. M. The metabolism of articular cartilage. Biochem J. 1940 Jul;34(7):1070–1077. doi: 10.1042/bj0341070. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holm S., Maroudas A., Urban J. P., Selstam G., Nachemson A. Nutrition of the intervertebral disc: solute transport and metabolism. Connect Tissue Res. 1981;8(2):101–119. doi: 10.3109/03008208109152130. [DOI] [PubMed] [Google Scholar]
- Jacoby R. K., Jayson M. I. Organ culture of adult human articular cartilage. I. The effect of hyperoxia on synthesis of glycosaminoglycan. J Rheumatol. 1975 Sep;2(3):270–279. [PubMed] [Google Scholar]
- Krebs H. A. The Pasteur effect and the relations between respiration and fermentation. Essays Biochem. 1972;8:1–34. [PubMed] [Google Scholar]
- Lane J. M., Brighton C. T., Menkowitz B. J. Anaerobic and aerobic metabolism in articular cartilage. J Rheumatol. 1977 Winter;4(4):334–342. [PubMed] [Google Scholar]
- MCILWAIN H. The effect of depressants on the metabolism of stimulated cerebral tissues. Biochem J. 1953 Feb;53(3):403–412. doi: 10.1042/bj0530403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marcus R. E. The effect of low oxygen concentration on growth, glycolysis, and sulfate incorporation by articular chondrocytes in monolayer culture. Arthritis Rheum. 1973 Sep-Oct;16(5):646–656. doi: 10.1002/art.1780160509. [DOI] [PubMed] [Google Scholar]
- Mason R. M., Sweeney C. The relationship between proteoglycan synthesis in Swarm chondrocytes and pathways of cellular energy and UDP-sugar metabolism. Carbohydr Res. 1994 Mar 4;255:255–270. doi: 10.1016/s0008-6215(00)90983-2. [DOI] [PubMed] [Google Scholar]
- McQuillan D. J., Handley C. J., Robinson H. C., Ng K., Tzaicos C., Brooks P. R., Lowther D. A. The relation of protein synthesis to chondroitin sulphate biosynthesis in cultured bovine cartilage. Biochem J. 1984 Dec 15;224(3):977–988. doi: 10.1042/bj2240977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mignotte F., Champagne A. M., Froger-Gaillard B., Benel L., Gueride M., Adolphe M., Mounolou J. C. Mitochondrial biogenesis in rabbit articular chondrocytes transferred to culture. Biol Cell. 1991;71(1-2):67–72. doi: 10.1016/0248-4900(91)90052-o. [DOI] [PubMed] [Google Scholar]
- Otte P. Basic cell metabolism of articular cartilage. Manometric studies. Z Rheumatol. 1991 Sep-Oct;50(5):304–312. [PubMed] [Google Scholar]
- Roberts S., Beard H. K., O'Brien J. P. Biochemical changes of intervertebral discs in patients with spondylolisthesis or with tears of the posterior annulus fibrosus. Ann Rheum Dis. 1982 Feb;41(1):78–85. doi: 10.1136/ard.41.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sampson H. W., Cannon M. S. Zonal analysis of metabolic profiles of articular-epiphyseal cartilage chondrocytes: a histochemical study. Histochem J. 1986 May;18(5):233–238. doi: 10.1007/BF01676232. [DOI] [PubMed] [Google Scholar]
- Silver I. A. Measurement of pH and ionic composition of pericellular sites. Philos Trans R Soc Lond B Biol Sci. 1975 Jul 17;271(912):261–272. doi: 10.1098/rstb.1975.0050. [DOI] [PubMed] [Google Scholar]
- Spencer C. A., Palmer T. N., Mason R. M. Intermediary metabolism in the Swarm rat chondrosarcoma chondrocyte. Biochem J. 1990 Feb 1;265(3):911–914. doi: 10.1042/bj2650911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TERNER C. Anaerobic and aerobic glycolysis in lactating mammary gland and in nervous tissue. Biochem J. 1952 Oct;52(2):229–237. doi: 10.1042/bj0520229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tushan F., Rodnan G. P., Altman M., Robin E. D. Anaerobic glycolysis and lactate dehydrogenase (LDH) isoenzymes in articular cartilage. J Lab Clin Med. 1969 Apr;73(4):649–656. [PubMed] [Google Scholar]
- Ysart G. E., Mason R. M. Responses of articular cartilage explant cultures to different oxygen tensions. Biochim Biophys Acta. 1994 Mar 10;1221(1):15–20. doi: 10.1016/0167-4889(94)90210-0. [DOI] [PubMed] [Google Scholar]