Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress

Xue Qing Wang, Ai Ying Xiao, Christian Sheline, Krzystztof Hyrc, Aizhen Yang, Mark P. Goldberg, Dennis W. Choi, Shan Ping Yu

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114 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2099-2110
Number of pages12
JournalJournal of cell science
Issue number10
StatePublished - May 15 2003


  • Apoptosis
  • K-ATPase
  • Na
  • Neuron
  • Potassium homeostasis

ASJC Scopus subject areas

  • Cell Biology


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