Heme-Regulated elF2 alpha Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Heme-Regulated elF2 alpha Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress
	Wang, Xiaoyan; Wang, Lixin; Liu, Sijin
刊名	CHEMICAL RESEARCH IN TOXICOLOGY
	2015-03
卷号	28 期号:3 页码:460-469
英文摘要	Lead (Pb) is a heavy metal with considerable environmental contamination. It is toxic to diverse cells and has been reported to cause :a wide array of detrimental health problems including neurological disorders and anemia. In light of the mechanisms underlying Pb-induced anemia, the current understanding is still limited, in spite of efforts for years. Our previous studies recognized a protective role for the heme-regulated eIF2 alpha kinase (Hri) in erythroid cells against oxidative stress exerted by arsenic and cadmium. Whether Hri is involved in Pb-induced hemolytic stress has not been scrutinized. In the current study, to more stringently address this question, we looked into erythropoiesis upon Pb(NO3)(2) exposure by using an in vivo mouse model and ex vivo cultured E14.5 fetal liver cells. Diagnoses of hemolytic anemia, decreased red cell count, reduced hemoglobin concentration, and elevated bilirubin level were Observed in Hri knockout (Ko) mice only, upon low-dose Pb administration. Significantly different from Ko mice, wild type (Wt) mice did not develop hei-nolytic anemia. Enforced extramedullary and medullary erythropoieses were found in Ko mice with Pb exposure. However, anemia was not compensated in Hri-deficient mice, as in-vivo and ex vivo results manifested that expanded Hri-null erythroid precursors experienced blocked differentiation and enhanced apoptosis, leading to ineffective erythropoiesis under Pb exposure. Additionally, Pb treatment also promoted hepcidin expression, and consequentially increased splenic iron storage, resulting in restrained iron availability for erythropoiesis. All erythroid precursors were prone to Pb-induced hemolytic stress. Hri deficiency gave rise to ineffective erythropoiesis and reduced iron availability for erythropoiesis under Pb stimulation, and these events together exacerbated Pb-induted hemolytic anemia. It is thus conceivable that this study delineated an indispensable function of Hri in maintaining red cell membrane integrity and guiding erythroid cell differentiation under Pb exposure. Our findings therefore deciphered a crucial role for Hri in protecting erythroid cells against Pb-induced toxieity.
研究领域[WOS]	Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology
WOS记录号	WOS:000351326400021
公开日期	2016-03-15
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/32589]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Wang, Xiaoyan,Wang, Lixin,Liu, Sijin. Heme-Regulated elF2 alpha Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2015,28(3):460-469.
APA	Wang, Xiaoyan,Wang, Lixin,&Liu, Sijin.(2015).Heme-Regulated elF2 alpha Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress.CHEMICAL RESEARCH IN TOXICOLOGY,28(3),460-469.
MLA	Wang, Xiaoyan,et al."Heme-Regulated elF2 alpha Kinase Plays a Crucial Role in Protecting Erythroid Cells against Pb-Induced Hemolytic Stress".CHEMICAL RESEARCH IN TOXICOLOGY 28.3(2015):460-469.