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Purine nucleosides: endogenous neuroprotectants in hypoxic brain
Version of Record online: 14 MAR 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 121, Issue 3, pages 329–342, May 2012
How to Cite
Thauerer, B., zur Nedden, S. and Baier-Bitterlich, G. (2012), Purine nucleosides: endogenous neuroprotectants in hypoxic brain. Journal of Neurochemistry, 121: 329–342. doi: 10.1111/j.1471-4159.2012.07692.x
- Issue online: 10 APR 2012
- Version of Record online: 14 MAR 2012
- Accepted manuscript online: 15 FEB 2012 03:27PM EST
- Received November 30, 2011; revised manuscript received February 2, 2012; accepted February 2, 2012.
- purine nucleosides
J. Neurochem. (2012) 121, 329–342.
Even a short blockade of oxygen flow in brain may lead to the inhibition of oxidative phosphorylation and depletion of cellular ATP, which results in profound deficiencies in cellular function. Following ischemia, dying, injured, and hypoxic cells release soluble purine-nucleotide and -nucleoside pools. Growing evidence suggests that purine nucleosides might act as trophic factors in the CNS and PNS. In addition to equilibrative nucleoside transporters (ENTs) regulating purine nucleoside concentrations intra- and extracellularly, specific extracellular receptor subtypes for these compounds are expressed on neurons, glia, and endothelial cells, mediating stunningly diverse effects. Such effects range from induction of cell differentiation, apoptosis, mitogenesis, and morphogenetic changes, to stimulation of synthesis and/or release of cytokines and neurotrophic factors under both physiological and pathological conditions. Multiple signaling pathways regulate the critical balance between cell death and survival in hypoxia–ischemia. A convergent pathway for the regulation of multiple modalities involved in O2 sensing is the mitogen activated protein kinase (p42/44 MAPK) or (ERK1/2 extracellular signal-regulated kinases) pathway terminating in a variety of transcription factors, for example, hypoxia-inducible factor 1α. In this review, the coherence of purine nucleoside-related pathways and MAPK activation in the endogenous neuroprotective regulation of the nervous system’s development and neuroplasticity under hypoxic stress will be discussed.