Downregulation of carnitine acyltransferases and organic cation transporter OCTN2 in mononuclear cells in healthy elderly and patients with myelodysplastic syndromes.
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.
Karlic
Heidrun
H
Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, H. Collinstrasse 30, 1140 Vienna, Austria. molzell@adis.at
Lohninger
Alfred
A
Laschan
Claudia
C
Lapin
Alexander
A
Böhmer
Franz
F
Huemer
Marlies
M
Guthann
Elisabeth
E
Rappold
Eduard
E
Pfeilstöcker
Michael
M
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000201:enzymology / Q000378:metabolism*; D002331:Carnitine / Q000097:blood; D002333:Carnitine Acyltransferases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074058:Solute Carrier Family 22 Member 5; D014158:Transcription, Genetic
D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine