Journal of Molecular Medicine

, Volume 81, Issue 7, pp 435–442

Downregulation of carnitine acyltransferases and organic cation transporter OCTN2 in mononuclear cells in healthy elderly and patients with myelodysplastic syndromes

  • Heidrun Karlic
  • Alfred Lohninger
  • Claudia Laschan
  • Alexander Lapin
  • Franz Böhmer
  • Marlies Huemer
  • Elisabeth Guthann
  • Eduard Rappold
  • Michael Pfeilstöcker
Original Article

DOI: 10.1007/s00109-003-0447-6

Cite this article as:
Karlic, H., Lohninger, A., Laschan, C. et al. J Mol Med (2003) 81: 435. doi:10.1007/s00109-003-0447-6

Abstract

Changes in key enzymes of oxidative metabolism at the mitochondrial level are known to be associated with the aging process, apoptosis, and many diseases. Considering the risk of acquiring a myelodysplastic syndrome (MDS) with age, the aim of this study was to quantify mRNA synthesis of the carnitine palmitoyltransferases (CPT1 and CPT2), carnitine acetyltransferase (CRAT), human specific microsomal CPT, and OCTN2 (organic cation transporter) in mononuclear cells of healthy humans of different age groups and MDS patients. Using quantitative reverse transcriptase real-time PCR we compared mRNA synthesis of the above mentioned enzymes in mononuclear cells from peripheral blood of 23 healthy persons (mean age 45 years), 9 blood and 22 bone marrow samples of 31 MDS patients with varying proportions of apoptotic cells (mean age 78 years), and blood samples of 30 age-matched controls. In addition, plasma carnitine levels were determined. Compared to younger adults, there was a 50% downregulation of CPT1 in elderly persons and in MDS patients. Reduction in CRAT, CPT 2, and OCTN2 was more than 85%. Reduction in microsomal CPT was more pronounced in MDS patients than in age-matched controls (96% vs. 43%). In MDS bone marrow cells there was a negative correlation of CPT1 and CRAT with the relative proportion of apoptotic cells. Plasma carnitine values were similar in all groups. The described reduction in transcription of different genes in blood cells which is well known in different tissues may reflect a systemic signaling process, associated with aging, apoptosis, and MDS.

Keywords

Carnitine acyltransferasesmRNA quantificationBlood cellsAgingMyelodysplastic syndromes

Abbreviations

CACT

Carnitine acylcarnitine translocase

CoA

Coenzyme A

CPT

Carnitine palmitoyltransferase

CRAT

Carnitine acetyltransferase

MDS

Myelodysplastic syndromes

MNC

Mononuclear cells

PDH

Pyruvate dehydrogenase

RTQPCR

Quantitative reverse transcriptase real-time polymerase chain reaction

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Heidrun Karlic
    • 1
  • Alfred Lohninger
    • 2
  • Claudia Laschan
    • 1
    • 3
  • Alexander Lapin
    • 4
  • Franz Böhmer
    • 4
  • Marlies Huemer
    • 1
    • 2
    • 5
  • Elisabeth Guthann
    • 1
  • Eduard Rappold
    • 6
  • Michael Pfeilstöcker
    • 1
    • 3
  1. 1.Ludwig Boltzmann Institute for Leukemia Research and HematologyHanusch HospitalViennaAustria
  2. 2.Department of Medical ChemistryUniversity of ViennaViennaAustria
  3. 3.3rd Medical DepartmentHanusch HospitalViennaAustria
  4. 4.Sozialmedizinisches Zentrum SophienspitalViennaAustria
  5. 5.Ludwig Boltzmann Institute for OsteologyViennaAustria
  6. 6.Otto Wagner HospitalViennaAustria