title: Activation of AMP-Activated Protein Kinase by Adenine Alleviates TNF-Alpha-Induced Inflammation in Human Umbilical Vein Endothelial Cells.
abstract: The AMP-activated protein kinase (AMPK) signaling system plays a key role in cellular stress by repressing the inflammatory responses induced by the nuclear factor-kappa B (NF-κB) system. Previous studies suggest that the anti-inflammatory role of AMPK involves activation by adenine, but the mechanism that allows adenine to produce these effects has not yet been elucidated. In human umbilical vein endothelial cells (HUVECs), adenine was observed to induce the phosphorylation of AMPK in both a time- and dose-dependent manner as well as its downstream target acetyl Co-A carboxylase (ACC). Adenine also attenuated NF-κB targeting of gene expression in a dose-dependent manner and decreased monocyte adhesion to HUVECs following tumor necrosis factor (TNF-α) treatment. The short hairpin RNA (shRNA) against AMPK α1 in HUVECs attenuated the adenine-induced inhibition of NF-κB activation in response to TNF-α, thereby suggesting that the anti-inflammatory role of adenine is mediated by AMPK. Following the knockdown of adenosyl phosphoribosyl transferase (APRT) in HUVECs, adenine supplementation failed to induce the phosphorylation of AMPK and ACC. Similarly, the expression of a shRNA against APRT nullified the anti-inflammatory effects of adenine in HUVECs. These results suggested that the role of adenine as an AMPK activator is related to catabolism by APRT, which increases the cellular AMP levels to activate AMPK.
authors.affiliation: Energenesis Biomedical Co., Ltd., New Taipei City, Taiwan.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Cheng
authors.affiliation: Energenesis Biomedical Co., Ltd., New Taipei City, Taiwan.
authors.forename: Guang-Huar
authors.initials: GH
authors.lastname: Young
authors.affiliation: Energenesis Biomedical Co., Ltd., New Taipei City, Taiwan.
authors.forename: Jiun-Tsai
authors.initials: JT
authors.lastname: Lin
authors.affiliation: Energenesis Biomedical Co., Ltd., New Taipei City, Taiwan.
authors.forename: Hyun-Hwa
authors.initials: HH
authors.lastname: Jang
authors.affiliation: Department of Life Science, Institute of Applied Science and Engineering, Catholic Fu-Jen University, New Taipei City, Taiwan.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Collage of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Nong
authors.affiliation: Energenesis Biomedical Co., Ltd., New Taipei City, Taiwan.
authors.forename: Po-Ku
authors.initials: PK
authors.lastname: Chen
authors.affiliation: Energenesis Biomedical Co., Ltd., New Taipei City, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Kuo
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Kao
authors.affiliation: Department of Life Science, Institute of Applied Science and Engineering, Catholic Fu-Jen University, New Taipei City, Taiwan.
authors.forename: Yao-Jen
authors.initials: YJ
authors.lastname: Liang
authors.affiliation: Department of Life Science, Institute of Applied Science and Engineering, Catholic Fu-Jen University, New Taipei City, Taiwan.
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000225:Adenine / Q000494:pharmacology* / Q000633:toxicity; D000228:Adenine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D014409:Tumor Necrosis Factor-alpha; D000620:Aminoimidazole Carboxamide; D000228:Adenine Phosphoribosyltransferase; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D000225:Adenine