naa a22 4500 510746276 CHVBK 20180411083047.0 cr unu---uuuuu 180411e20130901xx s 000 0 eng 10.1007/s12192-013-0416-0 doi (NATIONALLICENCE)springer-10.1007/s12192-013-0416-0 Inhibition of cystathionine β-synthase is associated with glucocorticoids over-secretion in psychological stress-induced hyperhomocystinemia rat liver [Elektronische Daten] [Yun Zhao, Shuqing Wu, Xiujie Gao, Zhiqing Zhang, Jingbo Gong, Rui Zhan, Xinxing Wang, Weiming Wang, Lingjia Qian] Hyperhomocysteinemia (HHcy), a pathological condition characterized by an increase in plasma concentration of total homocysteine (Hcy), is recognized as a risk factor for several diseases. The transsulfuration pathway is the main metabolic fate of Hcy utilization, which requires the activity of cystathionine β-synthase (CBS). Our results showed the development of HHcy induced by psychological stress was mainly derived from a reduction of CBS activity in the liver, which was accompanied by a significant decrease in its mRNA level. It suggested that the hepatic CBS enzyme regulated by stress at the level of transcription would have a profound effect on circulating Hcy levels. The expression of Sp3, a negative factor for cbs transcription, obviously increased in hepatocytes nuclei of stressed rats, but Sp1 was not altered. It indicated that Sp3 was the key point of variations in cbs transcription caused by stress. Meanwhile, we detected that augmented plasma Hcy concentrations correlated with glucocordicoids (GCs) over-secretion in response to stress, and CBS mRNA levels were markedly lowered in GCs-treated rat hepatocytes. Further results found that glucocorticoids receptor (GR) expression in hepatocyte nuclei of stress rats and GR nuclear translocation ratio was increased, and the same results were proved by experiments in vitro, i.e., GR nuclear translocation and Sp3 expression was remarkably increased in GCs-treated hepatocytes. Moreover, results from ChIP suggested GCs enhanced the binding of GR to the regulatory region of the Sp3 promoter. These results indicated that GCs inhibit CBS transcription by up-regulating Sp3 in psychological stress-induced HHcy. Cell Stress Society International, 2013 Homocysteine nationallicence Cystathionine β-synthase nationallicence Psychological stress nationallicence Hyperhomocysteinemia nationallicence Glucocordicoids nationallicence Sp 1/3 nationallicence HHcy : Hyperhomocysteinemia nationallicence Hcy : Homocysteine nationallicence CBS : Cystathionine β-synthase nationallicence Sp : Specificity Protein nationallicence GCs : Glucocordicoids nationallicence GR : Glucocorticoids receptor nationallicence GREs : Glucocorticoid response elements nationallicence Zhao Yun Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut Wu Shuqing Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut Gao Xiujie Institute of Health and Environmental Medicine, Tianjin, China aut Zhang Zhiqing Institute of Health and Environmental Medicine, Tianjin, China aut Gong Jingbo Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut Zhan Rui Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut Wang Xinxing Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut Wang Weiming Beijing University of Chinese Medicine, Beijing, China aut Qian Lingjia Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut Cell Stress and Chaperones Springer Netherlands 18/5(2013-09-01), 631-641 1355-8145 18:5<631 2013 18 12192 https://doi.org/10.1007/s12192-013-0416-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12192-013-0416-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhao Yun Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut NATIONALLICENCE 700 1- Wu Shuqing Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut NATIONALLICENCE 700 1- Gao Xiujie Institute of Health and Environmental Medicine, Tianjin, China aut NATIONALLICENCE 700 1- Zhang Zhiqing Institute of Health and Environmental Medicine, Tianjin, China aut NATIONALLICENCE 700 1- Gong Jingbo Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut NATIONALLICENCE 700 1- Zhan Rui Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut NATIONALLICENCE 700 1- Wang Xinxing Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut NATIONALLICENCE 700 1- Wang Weiming Beijing University of Chinese Medicine, Beijing, China aut NATIONALLICENCE 700 1- Qian Lingjia Key laboratory of stress medicine, Institute of Basic Medical Sciences, Beijing, China aut NATIONALLICENCE 773 0- Cell Stress and Chaperones Springer Netherlands 18/5(2013-09-01), 631-641 1355-8145 18:5<631 2013 18 12192 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer