Factors affecting the inhibition by alloxan, and effect of streptozotocin on phosphate transport in isolated mouse mitochondria
Tóm tắt
The swelling technique evidenced inhibition of Pi transport in isolated mouse liver mitochondria by 1 mM or higher concentration of alloxan, while no effect was found with streptozotocin. Complete or partial protection against alloxan inhibition was found under the following conditions: preincubation at 4 °C, or pretreatment with Pi, glucagon, succinate, malate or pyruvate. Complete protection was observed in isolated mitochondria from mice injected with glucagon. No protection was seen under the following conditions: preincubation at 37 °C, addition of microsomes, or pretreatment with insulin or glucagon in the presence of glucagon antibodies. So-called light and heavy mitochondria were as sensitive to alloxan as those obtained with the routine technique. Alloxanic acid had no effect, and addition of cysteine or glutathione abolished the inhibition by alloxan. Alloxan inhibited Pi transport also in isolated lung mitochondria. The findings suggest a direct action of alloxan on mitochondrial Pi transport which is affected by the energetic state. A relationship seems to exist between protection against alloxan toxicityin vivo and protection under the present experimental conditions.
Tài liệu tham khảo
Ammon H. P. T., Akhtar M. S., Grimm A., Niklas H.: Effect of methylene blue and thiol oxidants on pancreatic islet GSH/GSSG ratios and tolbutamide mediated insulin releasein vitro — Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak.307, 91, 1979.
Ammon H. P. T., Akhtar M. S., Niklas H., Hegner D.: Inhibition ofp-chloromercuribenzoate- and glucose-induced insulin releasein vitro by methylene blue, diamide, andtert-butyl hydroperoxide — Molec. Pharmacol.13, 598, 1977.
Arteta J. L., Carballido A.: The preventive effect of glucagon (HGF) against the diabetogenic action of alloxan and its antagonism by insulin — J. Endocr.15, 243, 1957.
Arteta J. L., König A., Carballido A.: The effects of glucose and insulin on the diabetogenic action of alloxan — J. Endocr.10, 342, 1954.
Barritt G. J., Thorne R. F. W., Hughes B. P.: Effects of hormones and N6O2-dibutyryl-adenosine 3′:5′-cyclic monophosphate, administeredin vivo, on phosphate transport and metabolism in isolated rat liver mitochondria — Biochem. J.172, 577, 1978.
Bhattacharya G.: Studies on the mechanism of the diabetogenic action of alloxan — Proc. nat. Inst. Sci. India (New Delhi)21, 210, 1955.
Boquist L.: Differences in the blood glucose response of mice to alloxan and alloxan-inhibiting compounds — Acta endocr. (Kbh.)92, 687, 1979.
Boquist L.: A new hypothesis for alloxan diabetes — Acta path. microbiol. scand. (Sect. A)88, 201, 1980.
Boquist L., Lorentzon R.: Study on the early blood glucose response of mice to alloxan — Diabète et Métab.6, 55, 1980.
Boquist L., Nelson L.: Effect of alloxan on phosphate transport in isolated mouse liver mitochondria — Med. Biol.59, 47, 1981.
Boquist L., Nelson L.: Inhibition by alloxan of mitochondrial anion transport — Upsala J. med. Sci.86, 183, 1981.
Boquist L., Nelson L.: Alloxan effect on phosphate transport in isolated mouse liver mitochondria: Influence of pH, and discrimination between phosphate influx and efflux — Diabète et Métab.8, 121, 1982.
Briand Y., Touraille S., Debrise R., Durand R.: Proteins dealing with N-ethylmaleimide inhibition of pig heart mitochondrial phosphate transport system — FEBS Letters65, 1, 1976.
Brükmann G., Wertheimer E.: Diabetogenic action of alloxan derivatives — Nature (Lond.)155, 267, 1945.
Cottrell T. S., Levine O. R., Senior R. M., Wiener J., Spiro D., Fishman A. P.: Electron microscopic alterations at the alveolar level in pulmonary edema — Circulat. Res.21, 783, 1967.
Dawson A. P.: Inhibition of mitochondrial phosphate transport byp-diazobenzene-sulphonate — Biochem. J.144, 597, 1974.
Grankvist K., Marklund S., Sehlin J., Täljedal I.-B.: Superoxide dismutase, catalase and scavengers of hydroxyl radical protect against the toxic action of alloxan on pancreatic islet cellsin vitro — Biochem J.182, 17, 1979.
Heikkila R. E., Barden H., Cohen G.: Prevention of alloxan-induced diabetes by ethanol administration — J. Pharmacol. exp. Ther.190, 501, 1974.
Lanoue K. F., Schoolwerth A. C.: Metabolite transport in mitochondria — Ann. Rev. Biochem.48, 871, 1979.
Klingenberg M., Durand R., Guérin B.: Analysis of the reactivity of SH-reagents with the mitochondrial phosphate carrier — Europ. J. Biochem.42, 135, 1974.
Lazarow A.: Protective effect of glutathione and cysteine against alloxan diabetes in the rat — Proc. Soc. exp. Biol. (N.Y.)61, 441, 1946.
LeQuoc D., LeQuoc K., Gaudemer Y.: Energy-dependent variation of thiol groups reactivity or accessibility in rat liver mitochondria, revealed by measurements of labelled thiol reagents incorporation — Biochem. biophys. Res. Commun.68, 106, 1976.
LeQuoc D., LeQuoc K., Gaudemer Y.: Influence of the energetic state of rat liver mitochondria on the sensitivity of the phosphate carrier towards SH reagents — Biochim. biophys. Acta (Amst.)462, 131, 1977.
Nelson L., Boquist L.: Effects of alloxan and streptozotocin on calcium transport in isolated mouse liver mitochondria — Cell. Calc.3, 191, 1982.
Patterson J. W., Lazarow A., Levey S.: Reactions of alloxan and dialuric acid with the sulfhydryl group — J. biol. Chem.177, 187, 1949.
Sabadie-Pialoux N., Abou-Khalil S., Gautheron D. C.: Discrimination by14C-6,6′-dithiodinicotinic acid between vicinal dithiols and single thiols implicated in mitochondrial membrane energy transduction — J. Microsc. Biol. Cell.26, 19, 1976.
Werringloer J., Estabrook R. W.: Heterogeneity of liver microsomal Cyt P-450: the spectral characterization of reactants with red Cyt P-450 — Arch. Biochem.167, 270, 1975.
Webb J. L.: Alloxan. In:Webb J.L. (Ed.): Enzyme and metabolic inhibitors, vol 3. Academic Press, New York, 1966; p. 367.
Younathan E. S.: Inhibition of the citric acid cycle by alloxan — J. biol. Chem.237, 608, 1962.
Zoccarato F., Rugolo M., Siliprandi D.: Phosphate transport in mitochondria and submitochondrial particles: the influence of thiol oxidation — J. Bioenerg. Biomembr.9, 203, 1977.