title: Neuroglobin Overexpression Inhibits AMPK Signaling and Promotes Cell Anabolism.
abstract: Neuroglobin (Ngb) is a recently discovered globin with preferential localization to neurons. Growing evidence indicates that Ngb has distinct physiological functions separate from the oxygen storage and transport roles of other globins, such as hemoglobin and myoglobin. We found increased ATP production and decreased glycolysis in Ngb-overexpressing immortalized murine hippocampal cell line (HT-22), in parallel with inhibition of AMP-activated protein kinase (AMPK) signaling and activation of acetyl-CoA carboxylase (ACC). In addition, lipid and glycogen content was increased in Ngb-overexpressing HT-22 cells. AMPK signaling was also inhibited in the brain and heart from Ngb-overexpressing transgenic mice. Although Ngb overexpression did not change glycogen content in whole brain, glycogen synthase was activated in cortical neurons of Ngb-overexpressing mouse brain and Ngb overexpression primary neurons. Moreover, lipid and glycogen content was increased in hearts derived from Ngb-overexpressing mice. These findings suggest that Ngb functions as a metabolic regulator and enhances cellular anabolism through the inhibition of AMPK signaling.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA.|Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, 94945, USA.
authors.forename: XiaoOu
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Winters
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA.
authors.forename: Myoung-Gwi
authors.initials: MG
authors.lastname: Ryou
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, 94945, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, China. ningwang@mail.fjmu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA. kunlin.jin@unthsc.edu.
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA. shaohua.yang@unthsc.edu.|Department of Neurosurgery, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China. shaohua.yang@unthsc.edu.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology; D004789:Enzyme Activation; D005914:Globins / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000633:toxicity; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008822:Mice, Transgenic; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism; D010100:Oxygen; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008055:Lipids; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D005914:Globins; D006003:Glycogen; D006006:Glycogen Synthase; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen
keywords: AMP-activated protein kinase (AMPK); Acetyl-CoA carboxylase (ACC); Anabolism; Glycogen synthase; Metabolism; Neuroglobin