TY - JOUR
T1 - PFOA and PFOS promote diabetic renal injury in vitro by impairing the metabolisms of amino acids and purines
AU - Gong, Xun
AU - Yang, Chunxue
AU - Hong, Yanjun
AU - Chung, Chi Kong Arthur
AU - Cai, Zongwei
N1 - Funding Information:
This work was supported by the grants from National Natural Science Foundation of China (General Program 21577115 and 21477101); the Research Grants Council, University Grants Committee of Hong Kong (RGC GRF 463612, 14104314, 12300114); Faculty Research Grants from the Hong Kong Baptist University (FRG2/15-16/067; FRG2/16-17/049; FRG2/17-18/072); Hong Kong Health and Medical Research Fund (HMRF/03144376); and HKASO research grant 2015-16.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Background: Environmental pollutants, perfluorooctanoic acid (PFOA)and perfluorooctane sulfonate (PFOS), are common surfactants in various consumer products. Epidemiological studies have demonstrated the association of diabetic kidney diseases with PFOA and PFOS. However, mechanisms of metabolic alterations involved are still unclear. Methods: Considering their involvement of glomerular hemodynamics, rat mesangial cells (MCs)are used as an in vitro model of diabetic kidney diseases for exposure to PFOS/PFOA under diabetic condition. Non-targeted metabolomics studies based on liquid chromatography-high resolution mass spectrometry were conducted to determine how PFOA/PFOS promoted fibrotic and proinflammatory responses in the MCs under diabetic condition. Results: Exposure of PFOA/PFOS (10 μM)increased oxidative stress and the levels of fibrotic and proinflammatory markers in MCs under diabetic condition. We demonstrated for the first time that PFOA and PFOS altered amino acid biosynthesis, citrate cycle, and purine metabolism in MCs under diabetic condition. Compared with diabetic condition, the exposure of PFOA and PFOS under diabetic condition more significantly altered the levels of 13 intracellular metabolites, including L-tyrosine, L-phenylalanine, L-arginine, L-tryptophan, AMP, ADP, UMP, inosine, and hypoxanthine, which have been reported to be related to kidney injury. In addition, PFOA/PFOS treatment significantly altered the expression levels of key enzymes involved in these metabolisms. Treatment with L-tyrosine, L-phenylalanine, L-arginine, and L-tryptophan reduced the levels of fibrotic and inflammatory markers induced by PFOA/PFOS. Conclusion: Our results suggest that under diabetic condition, exposure of PFOA or PFOS aggravated diabetic kidney injury in vitro by impairing metabolisms of amino acids and purines to induce more fibrosis and inflammation in MCs.
AB - Background: Environmental pollutants, perfluorooctanoic acid (PFOA)and perfluorooctane sulfonate (PFOS), are common surfactants in various consumer products. Epidemiological studies have demonstrated the association of diabetic kidney diseases with PFOA and PFOS. However, mechanisms of metabolic alterations involved are still unclear. Methods: Considering their involvement of glomerular hemodynamics, rat mesangial cells (MCs)are used as an in vitro model of diabetic kidney diseases for exposure to PFOS/PFOA under diabetic condition. Non-targeted metabolomics studies based on liquid chromatography-high resolution mass spectrometry were conducted to determine how PFOA/PFOS promoted fibrotic and proinflammatory responses in the MCs under diabetic condition. Results: Exposure of PFOA/PFOS (10 μM)increased oxidative stress and the levels of fibrotic and proinflammatory markers in MCs under diabetic condition. We demonstrated for the first time that PFOA and PFOS altered amino acid biosynthesis, citrate cycle, and purine metabolism in MCs under diabetic condition. Compared with diabetic condition, the exposure of PFOA and PFOS under diabetic condition more significantly altered the levels of 13 intracellular metabolites, including L-tyrosine, L-phenylalanine, L-arginine, L-tryptophan, AMP, ADP, UMP, inosine, and hypoxanthine, which have been reported to be related to kidney injury. In addition, PFOA/PFOS treatment significantly altered the expression levels of key enzymes involved in these metabolisms. Treatment with L-tyrosine, L-phenylalanine, L-arginine, and L-tryptophan reduced the levels of fibrotic and inflammatory markers induced by PFOA/PFOS. Conclusion: Our results suggest that under diabetic condition, exposure of PFOA or PFOS aggravated diabetic kidney injury in vitro by impairing metabolisms of amino acids and purines to induce more fibrosis and inflammation in MCs.
KW - Amino acid metabolism
KW - Fibrosis, diabetic kidney disease
KW - PFOA, PFOS
KW - Purine metabolism
UR - http://www.scopus.com/inward/record.url?scp=85064706225&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2019.04.208
DO - 10.1016/j.scitotenv.2019.04.208
M3 - Journal article
C2 - 31029902
AN - SCOPUS:85064706225
SN - 0048-9697
VL - 676
SP - 72
EP - 86
JO - Science of the Total Environment
JF - Science of the Total Environment
ER -
