Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat:How Does the Brain Breathe?  

作　　者：Chun-Yang Li Hai-Feng Jiang Li Li Xiao-Jing Lai Qian-Rong Liu Shang-Bin Yu Cheng-La Yi Xiao-Qian Chen 

机构地区：[1]Department of Pathophysiology,Tongji Medical College,Key Laboratory of Neurological Diseases,The Ministry of Education(HUST),Huazhong University of Science and Technology,Wuhan 430030,China [2]School of Life Science and Technology,Wuhan Polytechnic University,Wuhan 430023,China [3]Department of Traumatic Surgery,Tong-ji Hospital,Tong-ji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Neuroscience Bulletin》2023年第10期1481-1496,共16页神经科学通报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81972362,82173197,and 81672504).

摘　　要：The discovery of neuroglobin(Ngb),a brain-or neuron-specific member of the hemoglobin family,has revolutionized our understanding of brain oxygen metabolism.Currently,how Ngb plays such a role remains far from clear.Here,we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia.We found that Ngb was present in,co-localized to,and co-migrated with mitochondria in the cell body and neurites of neurons.Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane(CM)or cell surface in living neurons,and this was accompanied by the mitochondria.In vivo,hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio.Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase(SDH)and ATPase activity in neuronal N2a cells.Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia.Mutation of Ngb at its oxygen-binding site(His64)significantly increased SDH activity and reduced ATPase activity in N2a cells.Taken together,Ngb was physically and functionally linked to mitochondria.In response to an insufficient oxygen supply,Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation.This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer’s disease and diseases that cause hypoxia in the brain such as anemia.

关 键 词：NEUROGLOBIN HYPOXIA Ischemia ANEMIA Neuron ASTROCYTE 

分 类 号：R338[医药卫生—人体生理学]