Skip to main content

Advertisement

SpringerLink
Log in

Cardiolipin Synthase-1 mRNA Expression Does Not Correlate with Endogenous Cardiolipin Synthase Enzyme Activity In Vitro and In Vivo in Mammalian Lipopolysaccharide Models of Inflammation

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

We examined if lipopolysaccharide (LPS) treatment of mice affected cardiolipin (CL) synthesis. Mice were injected i.p. with LPS, the liver harvested, and CL synthase (CLS) enzyme activity and its mRNA expression examined. Treatment of mice with LPS resulted in a 55% decrease (p < 0.01) in mRNA expression of murine CLS compared to controls, but CLS enzyme activity was unaltered. The pool size of liver CL and other phospholipids were unaltered by LPS treatment. A similar effect was observed in murine epidermal fat pad and in vitro in RAW mouse macrophages and in human HepG2 cells. LPS treatment of HepG2 cells transiently expressing a histidine-tagged human cardiolipin synthase-1 (hCLS1) reduced hCLS1 mRNA and newly synthesized CLS activity indicating that LPS inhibits production of newly synthesized hCLS1 via reduction in hCLS1 mRNA. The results clearly indicate that CLS mRNA levels cannot be correlated with CLS enzyme activity nor CL content in the LPS model of inflammation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CL:

Cardiolipin

LPS:

Lipopolysaccharide

CLS:

Cardiolipin synthase

hCLS1:

Human cardiolipin synthase-1

mCLS1:

Murine cardiolipin synthase-1

FBS:

Fetal bovine serum

References

  1. Hostetler, K.Y. 1982. Polyglycerolphospholipids: phosphatidylglycerol, diphosphatidylglycerol and bis(monoacylglycero)phosphate. In Phospholipids, ed. J.N. Hawthorne and G.B. Ansell, 215–242. Amsterdam: Elsevier.

    Google Scholar 

  2. Hoch, F.L. 1992. Cardiolipins and biomembrane function. Biochimica et Biophysica Acta 1113: 71–133.

    PubMed  CAS  Google Scholar 

  3. Schlame, M., D. Rua, and M.L. Greenberg. 2000. The biosynthesis and functional role of cardiolipin. Progress in Lipid Research 39: 257–288.

    Article  PubMed  CAS  Google Scholar 

  4. Hatch, G.M. 2004. Cell biology of cardiac mitochondrial phospholipids. Biochemistry and Cell Biology 82: 99–112.

    Article  PubMed  CAS  Google Scholar 

  5. Zhang, M., E. Mileykovskaya, and W. Dowhan. 2002. Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial membrane. The Journal of Biological Chemistry 277: 43553–43556.

    Article  PubMed  CAS  Google Scholar 

  6. Esposti, M.D. 2002. Lipids, cardiolipin and apoptosis: a greasy license to kill. Cell Death and Differentiation 9: 234–236.

    Article  PubMed  Google Scholar 

  7. Garrido, C., L. Galluzzi, M. Brunet, P.E. Puig, C. Didelot, and G. Kroemer. 2006. Mechanisms of cytochrome c release from mitochondria. Cell Death and Differentiation 13: 1423–1433.

    Article  PubMed  CAS  Google Scholar 

  8. Ott, M., B. Zhivotovsky, and S. Orrenius. 2007. Role of cardiolipin in cytochrome c release from mitochondria. Cell Death and Differentiation 14: 1243–1247.

    Article  PubMed  CAS  Google Scholar 

  9. Hauff, K., and G.M. Hatch. 2006. Cardiolipin metabolism in Barth syndrome. Progress in Lipid Research 45: 91–101.

    Article  PubMed  CAS  Google Scholar 

  10. Schlame, M., and D. Haldar. 1993. Cardiolipin is synthesized on the matrix side of the inner membrane in rat liver mitochondria. The Journal of Biological Chemistry 268: 74–79.

    PubMed  CAS  Google Scholar 

  11. Hostetler, K.Y., H. Van Den Bosch, and L.L.M. Van Deenen. 1971. Biosynthesis of cardiolipin in liver mitochondria. Biochimica et Biophysica Acta 239: 113–119.

    PubMed  CAS  Google Scholar 

  12. Lu, B., F. Xu, Y.J. Jiang, P.C. Choy, G.M. Hatch, C. Grunfeld, and K.R. Feingold. 2006. Cloning and characterization of a gene encoding human cardiolipin synthase (hCLS1). Journal of Lipid Research 47: 1140–1145.

    Article  PubMed  CAS  Google Scholar 

  13. Houtkooper, R.H., H. Akbari, H. van Lenthe, W. Kulik, R.J.A. Wanders, M. Frentzen, and F.M. Vaz. 2006. Identification and characterization of human cardiolipin synthase. FEBS Letters 580: 3059–3064.

    Article  PubMed  CAS  Google Scholar 

  14. Chen, D., X.Y. Zhang, and Y. Shi. 2006. Identification and functional characterization of hCLS1, a human cardiolipin synthase localized in mitochondria. The Biochemical Journal 398: 169–176.

    Article  PubMed  CAS  Google Scholar 

  15. Choi, S.Y., F. Gonzalvez, G.M. Jenkins, C. Slomianny, D. Chretien, D. Arnoult, P.X. Petit, and M.A. Frohman. 2007. Cardiolipin deficiency releases cytochrome c from the inner mitochondrial membrane and accelerates stimuli-elicited apoptosis. Cell Death and Differentiation 14: 597–606.

    Article  PubMed  CAS  Google Scholar 

  16. Van, Q., J. Liu, B. Lu, K.R. Feingold, Y. Shi, R.M. Lee, and G.M. Hatch. 2007. Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and its resynthesis in growing HeLa cells. The Biochemical Journal 401: 103–109.

    Article  PubMed  CAS  Google Scholar 

  17. Coulouarn, C., G. Lefebvre, R. Daveau, F. Letellier, M. Hiron, L. Drouot, M. Daveau, and J.P. Salier. 2006. Hepatology 42: 946–955.

    Article  Google Scholar 

  18. Hatch, G.M., and G. McClarty. 1996. Regulation of cardiolipin biosynthesis in H9c2 cardiac myoblasts by cytidine 5′-triphosphate. The Journal of Biological Chemistry 271: 25810–25816.

    Article  PubMed  CAS  Google Scholar 

  19. Lu, B., A.H. Moser, J.K. Shigenaga, K.R. Feingold, and C. Grunfeld. 2006. Type II nuclear hormone receptors, coactivator, and target gene repression in adipose tissue in the acute-phase response. Journal of Lipid Research 47: 2179–2190.

    Article  PubMed  CAS  Google Scholar 

  20. Kazemi, M.R., C.M. McDonald, J.K. Shigenaga, C. Grunfeld, and K.R. Feingold. 2005. Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists. Arteriosclerosis, Thrombosis, and Vascular Biology 25: 1220–1224.

    Article  PubMed  CAS  Google Scholar 

  21. Webster, J., J.Y. Jiang, B. Lu, F.Y. Xu, W.A. Taylor, M. Mymin, M. Zhang, G.Y. Minuk, and G.M. Hatch. 2005. On the mechanism of the increase in cardiolipin biosynthesis and resynthesis in hepatocytes during rat liver regeneration. The Biochemical Journal 386: 137–143.

    Article  PubMed  CAS  Google Scholar 

  22. Rouser, G., S. Fleischer, and A. Yamamoto. 1970. Two dimensional thin layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 5: 494–496.

    Article  PubMed  CAS  Google Scholar 

  23. Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry 193: 265–275.

    PubMed  CAS  Google Scholar 

  24. White, D.A. 1973. The phospholipid composition of mammalian tissues. In Form and function of phospholipids, ed. G.B. Ansell, J.N. Hawthorne, and R.M.C. Dawson, 441–482. Amsterdam: Elsevier.

    Google Scholar 

  25. Funk, J.L., K.R. Feingold, A.H. Moser, and C. Grunfeld. 1993. Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation. Atherosclerosis 98: 67–82.

    Article  PubMed  CAS  Google Scholar 

  26. Kozlov, A.V., L. Gille, I. Miller, C. Piskernik, S. Haindl, K. Staniek, H. Nohl, S. Bahrami, W. Ohlinger, M. Gemeiner, and H. Redl. 2007. Opposite effects of endotoxin on mitochondrial and endoplasmic reticulum functions. Biochemical and Biophysical Research Communications 352: 91–96.

    Article  PubMed  CAS  Google Scholar 

  27. Hostetler, K.Y. 1991. Effect of thyroxine on the activity of mitochondrial cardiolipin synthase in rat liver. Biochimica et Biophysica Acta 1086: 139–140.

    PubMed  CAS  Google Scholar 

  28. Mutter, T., V.W. Dolinsky, B.J. Ma, W.A. Taylor, and G.M. Hatch. 2000. Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart. The Biochemical Journal 346: 403–406.

    Article  PubMed  CAS  Google Scholar 

  29. Taylor, W.A., F.Y. Xu, T.C. Mutter, B.J. Ma, V.W. Dolinsky, and G.M. Hatch. 2002. Expression of monolysocardiolipin acyltransferase activity is regulated in concert with the level of cardiolipin and cardiolipin biosynthesis in the mammalian heart. BMC Biochemistry 3: 9.

    Article  PubMed  Google Scholar 

  30. Schlame, M., and K.Y. Hostetler. 1991. Solubilization, purification, and characterization of cardiolipin synthase from rat liver mitochondria. Demonstration of its phospholipid requirement. The Journal of Biological Chemistry 266: 22398–22403.

    PubMed  CAS  Google Scholar 

Download references

Acknowlegements

This work was supported by operating grants from the Heart and Stroke Foundation of Manitoba, the Canadian Institutes of Health Research, and the Manitoba Health Research Council (G.M.H.) and the National Institutes of Health (K.R.F.). G.M.H. is a Canada Research Chair in Molecular Cardiolipin Metabolism.

Author information

Authors and Affiliations

  1. Department of Medicine, University of California, San Francisco, CA, 94121, USA

    Biao Lu & Kenneth R. Feingold

  2. Department of Dermatology, University of California, San Francisco, CA, 94121, USA

    Biao Lu & Kenneth R. Feingold

  3. Department of Pharmacology and Therapeutics, University of Manitoba, A307 Chown Building, 753 McDermot Avenue, Winnipeg, Manitoba, Canada, R3E 0T6

    Fred Y. Xu, William A. Taylor & Grant M. Hatch

  4. Department of Biochemistry and Medical Genetics, Internal Medicine and Center for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Canada, R3E 0T5

    Grant M. Hatch

Authors
  1. Biao Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fred Y. Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William A. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth R. Feingold
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Grant M. Hatch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Grant M. Hatch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, B., Xu, F.Y., Taylor, W.A. et al. Cardiolipin Synthase-1 mRNA Expression Does Not Correlate with Endogenous Cardiolipin Synthase Enzyme Activity In Vitro and In Vivo in Mammalian Lipopolysaccharide Models of Inflammation. Inflammation 34, 247–254 (2011). https://doi.org/10.1007/s10753-010-9230-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-010-9230-3

KEY WORDS

Search

Navigation