AGPAT (1-acyl-sn-glycerol 3-phosphate acyltransferase) exists in at least five isoforms in humans, termed as AGPAT1, AGPAT2, AGPAT3, AGPAT4 and AGPAT5. Although they catalyse the same biochemical reaction, their relative function, tissue expression and regulation are poorly understood. Linkage studies in humans have revealed that AGPAT2 contributes to glycerolipid synthesis and plays an important role in regulating lipid metabolism. We report the molecular cloning, tissue distribution, and enzyme characterization of mAGPATs (murine AGPATs) and regulation of cardiac mAGPATs by PPARα (peroxisome-proliferator-activated receptor α). mAGPATs demonstrated differential tissue expression profiles: mAGPAT1 and mAGPAT3 were ubiquitously expressed in most tissues, whereas mAGPAT2, mAGPAT4 and mAGPAT5 were expressed in a tissue-specific manner. mAGPAT2 expressed in in vitro transcription and translation reactions and in transfected COS-1 cells exhibited specificity for 1-acyl-sn-glycerol 3-phosphate. When amino acid sequences of five mAGPATs were compared, three highly conserved motifs were identified, including one novel motif/pattern KX2LX6GX12R. Cardiac mAGPAT activities were 25% lower (P<0.05) in PPARα null mice compared with wild-type. In addition, cardiac mAGPAT activities were 50% lower (P<0.05) in PPARα null mice fed clofibrate compared with clofibrate fed wild-type animals. This modulation of AGPAT activity was accompanied by significant enhancement/reduction of the mRNA levels of mAGPAT3/mAGPAT2 respectively. Finally, mRNA expression of cardiac mAGPAT3 appeared to be regulated by PPARα activation. We conclude that cardiac mAGPAT activity may be regulated by both the composition of mAGPAT isoforms and the levels of each isoform.
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January 2005
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Research Article|
January 07 2005
Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart
Biao LU;
Biao LU
*Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
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Yan J. JIANG;
Yan J. JIANG
†Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
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Yaling ZHOU;
Yaling ZHOU
*Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
‡Center for Research and Treatment of Atherosclerosis, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
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Fred Y. XU;
Fred Y. XU
†Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
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Grant M. HATCH;
Grant M. HATCH
1
†Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
‡Center for Research and Treatment of Atherosclerosis, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
1To whom correspondence should be addressed, at Department of Pharmacology and Therapeutics (email [email protected]).
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Patrick C. CHOY
Patrick C. CHOY
*Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
‡Center for Research and Treatment of Atherosclerosis, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6
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Publisher: Portland Press Ltd
Received:
August 06 2004
Revision Received:
September 09 2004
Accepted:
September 15 2004
Accepted Manuscript online:
September 15 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 385 (2): 469–477.
Article history
Received:
August 06 2004
Revision Received:
September 09 2004
Accepted:
September 15 2004
Accepted Manuscript online:
September 15 2004
Citation
Biao LU, Yan J. JIANG, Yaling ZHOU, Fred Y. XU, Grant M. HATCH, Patrick C. CHOY; Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart. Biochem J 15 January 2005; 385 (2): 469–477. doi: https://doi.org/10.1042/BJ20041348
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