Role of oxidative stress and caspase 3 in CD47-mediated neuronal cell death.
CD47 or integrin-associated protein promotes cell death in blood and tumor cells. Recently, CD47 signaling has been identified in neurons as well. In this study, we investigated the role of CD47 in neuronal cell death. Exposure of primary mouse cortical neurons to the CD47 ligand thrombospondin-1 or the specific CD47-activating peptide 4N1K induced cell death. Activation of CD47 elevated levels of active caspase 3 and increased the generation of reactive oxygen species (ROS) in a time-dependent manner. Both ROS scavengers and caspase inhibitors attenuated cell death. But ROS scavenging did not reduce the activation of caspase 3, and combination treatments with a caspase inhibitor plus free radical scavenger did not yield additive protection. Taken together, these data suggest that parallel and redundant pathways of oxidative stress and caspase-mediated cell death are involved. We conclude that CD47 mediates neuronal cell death through caspase-dependent and caspase-independent pathways.
Xing
Changhong
C
Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, MA 02129, USA.
Lee
Sunryung
S
Kim
Woo Jean
WJ
Jin
Guang
G
Yang
Yong-Guang
YG
Ji
Xunming
X
Wang
Xiaoying
X
Lo
Eng H
EH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D051928:CD47 Antigen / Q000276:immunology / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D019700:Thrombospondin 1 / Q000494:pharmacology; D013997:Time Factors
C120273:4N1K peptide; D000906:Antibodies; D000975:Antioxidants; D051928:CD47 Antigen; D061945:Caspase Inhibitors; D002839:Chromans; D009842:Oligopeptides; D010879:Piperazines; D017382:Reactive Oxygen Species; D019700:Thrombospondin 1; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C066382:U 78517F; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3