tailieunhanh - Báo cáo khoa hoc : Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats

The kynurenine pathway of tryptophan catabolism plays an important role in several biological systems affected by aging. We quantified tryptophan and its metabolites kynurenine (KYN), kynurenine acid (KYNA), picolinic acid (PIC) and quinolinic acid (QUIN), and activity of the kynurenine pathway enzymes indoleamine 2,3-dioxygenase | IFEBS Journal Changes in kynurenine pathway metabolism in the brain liver and kidney of aged female Wistar rats Nady Braidy1 Gilles J. Guillemin1 2 Hussein Mansour3 Tailoi Chan-Ling3 and Ross Grant1 4 1 University of New South Wales Faculty of Medicine Sydney NSW Australia 2 St Vincent s Centre for Applied MedicalResearch Sydney NSW Australia 3 Retinaland DevelopmentalNeurobiology Laboratory Discipline of Anatomy and Histology Schoolof MedicalSciences University of Sydney NSW Australia 4 Australasian Research Institute Sydney Adventist Hospital NSW Australia Keywords aging indoleamine 2 3-dioxygenase IDO kynurenine pathway NAD tryptophan Correspondence R. Grant Department of Pharmacology Faculty of Medicine University of NSW Sydney NSW 2052 Australia Fax 9385 1059 Tel 9385 3742 E-mail Received 18 March 2011 revised 6 August 2011 accepted 22 September 2011 doi The kynurenine pathway of tryptophan catabolism plays an important role in several biological systems affected by aging. We quantified tryptophan and its metabolites kynurenine KYN kynurenine acid KYNA picolinic acid PIC and quinolinic acid QUIN and activity of the kynurenine pathway enzymes indoleamine 2 3-dioxygenase IDO tryptophan 2 3-dioxygenase TDO and quinolinic acid phosphoribosyltransferase QPRTase in the brain liver and kidney of young middle-aged and old female Wistar rats. Tryptophan levels and TDO activity decreased in all tissues with age. In contrast brain IDO activity increased with age while liver and kidney IDO activity decreased with age. The levels of KYN KYNA QUIN and PIC in brain all increased with age while the levels of KYN in the liver and kidney showed a tendency to decrease. The levels of KYNA in the liver did not change but the levels of KYNA in the kidney increased. The levels of PIC and QUIN increased significantly in the liver but showed a tendency to decrease in the kidney. QPRTase activity in both brain and liver decreased .