title: Corticosterone increases intracellular Zn(2+) release in hippocampal HT-22 cells.
abstract: The previous studies suggested that the hippocampal zinc dyshomeostasis and high glucocorticoid level might hurt hippocampal function. However, the effect of corticosterone (CORT) on hippocampus zinc homeostasis is not fully characterized. In this study, we investigated the intracellular Zn(2+) concentration in hippocampal HT-22 cells after CORT treatment. The cells were incubated with 10μM CORT for 0h-24h, 0μM-50μM CORT for 6h and 2.5μM glucocorticoid receptor antagonist RU486 administered 30min before CORT application. The results showed that 10μM CORT increased the intracellular Zn(2+) level after 6h, which was diminished by 2.5μM RU486. Co-treatment of ZnSO4 and CORT augmented the increase in Zn(2+) level. TPEN, a membrane-permeable chelator for intracellular Zn(2+) greatly attenuated the Zn(2+) increase by CORT, while DTPA, a chelator for extracellular Zn(2+), had no same effects. CCK-8 tests demonstrated that 10μM CORT treatment for 6h had no inhibition effect on cells. However, intracellular reactive oxygen species (ROS) production increased and adenosine triphosphate (ATP) level decreased significantly after same CORT treatment, which was corrected by TPEN and aggravated by ZnSO4. It could be suggested that the increased intracellular Zn(2+) by CORT was greatly dependent on intracellular Zn(2+) release, but not extracellular Zn(2+) intake. Meanwhile, our results demonstrated that increased intracellular Zn(2+) by CORT resulted in ROS generation and decreased ATP level in cells, which have possible roles in the hippocampal function disorder induced by stress.
authors.affiliation: Department of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Junlong
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Mo
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, No. 411Hospital, 15 East Dongjiangwan Road, Shanghai 200081, China. Electronic address: wangshi411hospital@126.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Electronic address: shenhuicn@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002614:Chelating Agents / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D005938:Glucocorticoids; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D015032:Zinc; D003345:Corticosterone
keywords: Adenosine triphosphate; Corticosterone; Hippocampus; Intracellular Zn(2+); Reactive oxygen species