首页|Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat:How Does the Brain Breathe?
Neuroglobin Facilitates Neuronal Oxygenation through Tropic Migration under Hypoxia or Anemia in Rat:How Does the Brain Breathe?
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The discovery of neuroglobin(Ngb),a brain-or neuron-specific member of the hemoglobin family,has revolutionized our understanding of brain oxygen metab-olism.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 promi-nent migration of Ngb towards the cytoplasmic membrane(CM)or cell surface in living neurons,and this was accom-panied 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)signifi-cantly increased SDH activity and reduced ATPase activ-ity in N2a cells.Taken together,Ngb was physically and functionally linked to mitochondria.In response to an insuf-ficient oxygen supply,Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation.This novel mecha-nism 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.
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
School of Life Science and Technology,Wuhan Polytechnic University,Wuhan 430023,China
Department of Traumatic Surgery,Tong-ji Hospital,Tong-ji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China
National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China
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