Journal
JOURNAL OF CELL SCIENCE
Volume 116, Issue 10, Pages 2099-2110Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.00420
Keywords
Na+,K+-ATPase; apoptosis; potassium homeostasis; neuron
Categories
Funding
- NINDS NIH HHS [NS42236-01, NS 32636, R01 NS030337, NS 30337] Funding Source: Medline
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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 I-pump was time-dependently suppressed by apoptotic insults including serum deprivation, staurosporine, and C-2-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.
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