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

Research output: Contribution to journalArticle

105 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2099-2110
Number of pages12
JournalJournal of Cell Science
Volume116
Issue number10
DOIs
StatePublished - May 15 2003

Fingerprint

Oxidants
Reactive Oxygen Species
Adenosine Triphosphate
Apoptosis
Staurosporine
Succinic Acid
Serum
Pyruvic Acid
Homeostasis
Ions
Neurons
Membranes
sodium-translocating ATPase

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress. / Wang, Xue Qing; Xiao, Ai Ying; Sheline, Christian; Hyrc, Krzystztof; Yang, Aizhen; Goldberg, Mark P.; Choi, Dennis W.; Yu, Shan Ping.

In: Journal of Cell Science, Vol. 116, No. 10, 15.05.2003, p. 2099-2110.

Research output: Contribution to journalArticle

Wang, Xue Qing ; Xiao, Ai Ying ; Sheline, Christian ; Hyrc, Krzystztof ; Yang, Aizhen ; Goldberg, Mark P. ; Choi, Dennis W. ; Yu, Shan Ping. / Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress. In: Journal of Cell Science. 2003 ; Vol. 116, No. 10. pp. 2099-2110.
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