title: Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress.
abstract: The Na+, K+-ATPase (Na+, K+-pump) plays critical roles in maintaining ion homeostasis. Blocking the Na+, K+-pump may lead to apoptosis. By contrast, whether an apoptotic insult may affect the Na+, K+-pump activity is largely undefined. In cultured cortical neurons, the Na+, K+-pump activity measured as a membrane current Ipump was time-dependently suppressed by apoptotic insults including serum deprivation, staurosporine, and C2-ceramide, concomitant with depletion of intracellular ATP and production of reactive oxygen species. Signifying a putative relationship among these events, Ipump was highly sensitive to changes in ATP and reactive oxygen species levels. Moreover, the apoptosis-associated Na+, K+-pump failure and serum deprivation-induced neuronal death were antagonized by pyruvate and succinate in ATP- and reactive-oxygen-species-dependent manners. We suggest that failure of the Na+, K+-pump as a result of a combination of energy deficiency and production of reactive oxygen species is a common event in the apoptotic cascade; preserving the pump activity provides a neuroprotective strategy in certain pathological conditions.
authors.affiliation: Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Xue Qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Ai Ying
authors.initials: AY
authors.lastname: Xiao
authors.forename: Christian
authors.initials: C
authors.lastname: Sheline
authors.forename: Krzystztof
authors.initials: K
authors.lastname: Hyrc
authors.forename: Aizhen
authors.initials: A
authors.lastname: Yang
authors.forename: Mark P
authors.initials: MP
authors.lastname: Goldberg
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Choi
authors.forename: Shan Ping
authors.initials: SP
authors.lastname: Yu
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016923:Cell Death; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D011233:Precipitin Tests; D019289:Pyruvic Acid / Q000494:pharmacology; D017382:Reactive Oxygen Species; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D019802:Succinic Acid / Q000494:pharmacology; D013997:Time Factors
chemical_list: C064769:N-acetylsphingosine; D017382:Reactive Oxygen Species; D000244:Adenosine Diphosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D019311:Staurosporine; D013110:Sphingosine