期刊
TOXICOLOGICAL SCIENCES
卷 88, 期 1, 页码 274-283出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfi290
关键词
erythrocyte; hemoglobin; hemolytic anemia; lipid peroxidation; phosphatidylserine translocation; reactive oxygen species
类别
资金
- NCI NIH HHS [CA77839] Funding Source: Medline
- NCRR NIH HHS [RR01070, C06 RR015455] Funding Source: Medline
- NIAID NIH HHS [AI46424] Funding Source: Medline
- NIDDK NIH HHS [DK48831] Funding Source: Medline
- NIGMS NIH HHS [GM15431] Funding Source: Medline
Lipid peroxidation and the accompanying translocation of phosphatidylserine (PS) from the inner to the outer leaflet of the lipid bilayer have recently been identified as key components of a signaling pathway for phagocytosis of apoptotic cells by macrophages. Drug-induced hemolytic anemia has long been known to be caused by an accelerated uptake of damaged (but intact) erythrocytes by macrophages in the spleen, and this process has been associated with enhanced formation of reactive oxygen species (ROS). However, the role of lipid peroxidation in hemolytic injury has remained unclear, and the effect of hemolytic agents on the distribution of PS in the erythrocyte membrane is unknown. The present studies were undertaken to determine whether lipid peroxidation and PS translocation could be detected in rat and human erythrocytes by three types of direct-acting hemolytic agents-dapsone hydroxylamine, divicine hydroquinone, and phenylhydrazine. 2',7'-Dichlorodihydrofluorescein diacetate was employed as a probe for intracellular ROS formation; lipid peroxidation was assessed by GC/MS analysis of F-2-isoprostanes; and PS externalization was measured by annexin V labeling and the prothrombinase assay. The data confirmed that all three hemolytic agents generate ROS within erythrocytes under hemolytic conditions; however, no evidence for lipid peroxidation or PS translocation was detected. Instead, ROS production by these hemolytic agents was associated with extensive binding of oxidized and denatured hemoglobin to the membrane cytoskeleton. The data suggest that the transmembrane signal for macrophage recognition of hemolytic injury may be derived from oxidative alterations to erythrocyte proteins rather than to membrane lipids.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据