caa a22 4500 606235000 CHVBK 20210128101240.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2202-4 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2202-4 Asymmetric dimethylarginine triggers macrophage apoptosis via the endoplasmic reticulum stress pathway [Elektronische Daten] [Dan Hong, Hai-Chao Gao, Xiang Wang, Ling-Fang Li, Chuan-Chang Li, Ying Luo, Kang-Kai Wang, Yong-Ping Bai, Guo-Gang Zhang] Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is emerging as a key contributing factor in atherogenesis, a process in turn known to involve macrophage apoptosis. The aim of this study was to determine the effect of ADMA on macrophage apoptosis, with specific reference to the endoplasmic reticulum (ER) stress pathway. Macrophage apoptosis was evaluated by Annexin V- Propidium iodide (PI) and Hoechst 33258 staining assays. Levels of the ER stress marker glucose regulated protein 78 (GRP78) were characterized by western blot. Levels of the proapoptotic C/EBP-homologous protein (CHOP) were evaluated by western blot and reverse transcription polymerase chain reaction (RT-PCR), and caspase-4 activity was measured using a colorimetric protease assay kit. We observed ADMA dose- and time-dependent increases in macrophage levels of GRP78. Similar ADMA dose- and time-dependent increases were detected in intracellular caspase-4 activity and macrophage apoptosis, all of which were sensitive to treatment with siRNAs for protein kinase RNA-like ER kinase and inositol-requiring protein-1 (IRE1), the ADMA antagonist l-arginine, as well as inhibitors of eukaryotic translation initiation factor-2 (salubrinal), IRE1 (irestatin 9389), and c-Jun N-terminal kinase (SP600125). Our results indicate that ADMA triggers macrophage apoptosis via the ER stress pathway. Springer Science+Business Media New York, 2014 Asymmetric dimethylarginine nationallicence Endoplasmic reticulum stress nationallicence Apoptosis nationallicence Macrophages nationallicence Hong Dan Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut Gao Hai-Chao Department of Cardiovascular Medicine, The affiliated hospital of chengde medical college, 067000, Chengde, China aut Wang Xiang Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut Li Ling-Fang Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut Li Chuan-Chang Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut Luo Ying Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut Wang Kang-Kai Department of Pathophysiology, Xiangya School of Medicine, Central South University, 410078, Changsha, China aut Bai Yong-Ping Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut Zhang Guo-Gang Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 31-38 0300-8177 398:1-2<31 2015 398 11010 https://doi.org/10.1007/s11010-014-2202-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2202-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hong Dan Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut NATIONALLICENCE 700 1- Gao Hai-Chao Department of Cardiovascular Medicine, The affiliated hospital of chengde medical college, 067000, Chengde, China aut NATIONALLICENCE 700 1- Wang Xiang Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut NATIONALLICENCE 700 1- Li Ling-Fang Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut NATIONALLICENCE 700 1- Li Chuan-Chang Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut NATIONALLICENCE 700 1- Luo Ying Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut NATIONALLICENCE 700 1- Wang Kang-Kai Department of Pathophysiology, Xiangya School of Medicine, Central South University, 410078, Changsha, China aut NATIONALLICENCE 700 1- Bai Yong-Ping Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut NATIONALLICENCE 700 1- Zhang Guo-Gang Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#, 410078, Changsha, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 31-38 0300-8177 398:1-2<31 2015 398 11010