2024-03-29T14:16:59Z
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2022-12-14T04:19:34Z
461:462
The AGP-PPAR gamma axis promotes oxidative stress and diabetic endothelial cell dysfunction
Tsukahara, Ryoko
Haniu, Hisao
Matsuda, Yoshikazu
Tsukahara, Tamotsu
Diabetes
eNOS
NO
Alkyl-glycerophosphate
PPAR gamma
Alkyl-glycerophosphate (AGP) accumulates in atherogenic oxidized-LDL and human atherosclerotic plaques and is a potent agonist of peroxisome-proliferator-activated receptor-gamma (PPAR gamma). Recent studies suggest a potential regulatory role for PPAR gamma in endothelial nitric oxide synthase (eNOS) expression/activation and nitrogen oxide (NO) generation in the vascular endothelium. Importantly, eNOS-induced NO and advanced glycation end-products (AGEs) are involved in blood-vessel damage, and diabetic patients exhibit high serum NO and AGE levels; however, the effect of AGP on NO- and AGE-mediated endothelium dysfunction remains unknown. Investigation of the AGP-specific effects on NO- and AGE-mediated dysfunction and the underlying molecular mechanisms revealed that AGP upregulated eNOS expression and NO production, and that eNOS silencing and gamma antagonism inhibited AGP-mediated eNOS upregulation and NO production. Moreover, AGP-PPAR gamma-axis-mediated NO production promoted the generation of reactive oxygen species and AGE formation. These results suggested that AGP plays a significant role in the initiation/progression of diabetes-related atherosclerosis through PPAR gamma activation. (C) 2018 Elsevier B.V. All rights reserved.
Article
MOLECULAR AND CELLULAR ENDOCRINOLOGY. 473:100-113 (2018)
journal article
ELSEVIER IRELAND LTD
2018-09-15
application/pdf
MOLECULAR AND CELLULAR ENDOCRINOLOGY
473
100
113
0303-7207
AA00745811
https://soar-ir.repo.nii.ac.jp/record/21726/files/MOL_CELL_ENDOCRINOL-473-100.pdf
eng
29355589
https://pubmed.ncbi.nlm.nih.gov/29355589
10.1016/j.mce.2018.01.008
https://doi.org/10.1016/j.mce.2018.01.008
©2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/