Skip to main content
Log in

Uncoupler-and hypoxia-induced damage in the working rat heart and its treatment

I. Observations with uncouplers of oxidative phosphorylation

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

In the isolated working rat heart, the damaging effect of 0.05–0.06 μM Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone (FCCP) was reversible within 20 sec by perfusion with fresh buffer. Cysteine 3 mM restored the aortic flow to the initial value within an additional 15–20 sec. Thereafter, the FCCP effect became irreversible due to a progressive structural membrane change. The structural change by FCCP is probably brought about by ‘internalization’ of polar groups (R-SH; R−NH3 +) of the mitochondrial (and other) membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bereiter-Hahn J (1976) Dimethylaminostyrylmethylpyridiniumiodine (DASPMI) as a fluorescent probe for mitochondria in situ. Biochim Biophys Acta 423:1–14

    PubMed  Google Scholar 

  2. Drobnica L, Sturdik E (1979) The reaction of carbonylcyanidephenylhydrazones with thiols, Biochem Biophys Acta 585:462–476.

    PubMed  Google Scholar 

  3. Foucher B, Gaudemer Y (1971), Specification of SH-groups in the mitochondrial energy coupling system, revealed by measurements of14C ethacrynate incorporation into rat liver mitochondria. FEBS Letters 13:95–97

    PubMed  Google Scholar 

  4. Heil BM, Bereiter-Hahn J, Zimmer G (1982) NADH, flavoprotein and 2-(4-(Dimethylamino)styryl)-1-methyl-pyridinium Iodide (DASPMI) fluorescence at the surface of the isolated working rat heart. Z Physiol Chem 363:912

    Google Scholar 

  5. Heytler PG (1963) Uncoupling of oxidative phosphorylation by carbonylcyanide phenylhydrazones. I. Some characteristics of m-Cl-CCP action on mitochondria and chloroplasts. Biochemistry 2:357–361

    PubMed  Google Scholar 

  6. Heytler PG (1979) Uncouplers of oxidative phosphorylation, in Methods in Enzymology, vol LV (Fleischer S, Packer L) Academic Press, New York San Francisco London pp 462–472

    Google Scholar 

  7. Hobson Mills W, Jackson Porn W (1922), 2p Dimethylstyrylpyridinium-methiodide, a new photographic sensitizer. J Chem Soc 57:946–947

    Google Scholar 

  8. Krebs HA, Henseleit K (1932) Untersuchungen über die Harnstoffbildung im Tierkörper. Z Physiol Chem 210:33–66

    Google Scholar 

  9. Kyogoku Y, Yoshikawa K, Terada H (1980) Hydration water in mitochondrial suspensions. In: Pullmann B, Yagi K (eds) Water and metal cations in biological systems. Japan Scientific Societies Press, Tokyo, pp 129–134

    Google Scholar 

  10. Langendorff O (1895) Untersuchungen am lebenden Säugetierherzen. Arch Ges Physiol 61:291–332

    Google Scholar 

  11. Lochner A, Kotze JCN, Benade AJS, Gevers W (1978) Mitochondrial oxidative phosphorylation in low-flow hypoxia: Role of free fatty acids. J Mol Cell Cardiol 10:857–875

    PubMed  Google Scholar 

  12. Lochner A, Kotze JCN, Gevers W, Benade AJS (1979) Substrate effects on mitochondrial function and tissue lipids in low-flow hypoxia of isolated perfused rat hearts. Basic Res Cardiol 74:303–312

    PubMed  Google Scholar 

  13. Manella CA, Parsons DF (1977) Uncoupler induced changes in mitochondrial structure detected by small angle X-ray scattering. Biochim Biophys Acta 460:375.

    PubMed  Google Scholar 

  14. Neely JR, Liebermeister H, Battersby EJ, Morgan HE (1967) Effect of pressure development on oxygen consumption by isolated rat heart. Amer J Physiol 212:804–814

    PubMed  Google Scholar 

  15. Philips AP (1947) Condensation of aromatic aldehydes with α-Picoline methiodide. Organ Chem 12:333–341

    Google Scholar 

  16. Sabadie-Pialoux N, Gautheron DC (1971) Free SH variations during ATP synthesis by oxidative phosphorylation in heart muscle mitochondria. Biochim Biophys Acta 234:9–15

    PubMed  Google Scholar 

  17. Schapendonk HCM, Hemrika-Wagner AM, Theuvenet APR, Wong Fong Sang HW, Vredenberg WJR, Kraayenhof R (1980) Energy dependent changes of the electrokinetic properties of chloroplasts. Biochemistry 19:1922

    PubMed  Google Scholar 

  18. Shiuan D, Tu SI (1978) Fluorescent labeling of mitoplast membrane, effect of oxidative Phosphorylation uncouplers. Biochemistry 17:2249–2252

    PubMed  Google Scholar 

  19. Sungchul J, Nishiki B, Smith K, Rich T (1979) Micro light guides: a new method for measuring tissue fluorescence and reflectance. Amer J Physiol 236:C144-C156

    PubMed  Google Scholar 

  20. Taegtmeyer H, Hems R, Krebs HA (1980) Utilization of energy providing substrates in the isolated working rat heart. Biochem J 186:701–711

    PubMed  Google Scholar 

  21. Terada H (1981) The interaction of highly active uncouplers with mitochondria. Biochim Biophys Acta 639:225–242

    PubMed  Google Scholar 

  22. Wang JH, Copeland L (1974) Chemical modification of mitochondria, uncoupler binding by mitochondria in different metabolic states. Arch Biochem Biophys 162:64–72

    PubMed  Google Scholar 

  23. Zimmer G, Keith AD, Packer L (1972) Effect of sucrose and uncouplers on lipid spin labeling of mitochondria. Arch Biochem Biophys 152:105–113

    PubMed  Google Scholar 

  24. Zimmer G (1977) Carbonylcyanide p-trifluoro-methoxyphenyl-hydrazone-induced change of mitochondrial membrane structure revealed by lipid and protein spin labeling. Arch Biochem Biophys 181:26–32

    PubMed  Google Scholar 

  25. Zimmer G (1984) Fluidity of cell membranes in the presence of some drugs and inhibitors. In: Kates M, Manson LA (eds) Membrane Fluidity, vol 12 of Biomembranes, Chapter 5, Plenum Publishing Co, New York, pp 169–203

    Google Scholar 

  26. Zimmer G, Mainka L, Berger I (1979) 2-Mercaptopropionylglycin restores activity of oligomycinsensitive ATPase to control value following treatment with carbonylcyanide-trifluoro-methoxyphenylhydrazone. FEBS Letter 107:217–221

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by the Deutsche Forschungsgemeinschaft, Zi 80/17

Rights and permissions

Reprints and permissions

About this article

Cite this article

Veit, P., Fuchs, J. & Zimmer, G. Uncoupler-and hypoxia-induced damage in the working rat heart and its treatment. Basic Res Cardiol 80, 107–115 (1985). https://doi.org/10.1007/BF01910457

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01910457

Key Words

Navigation