title: Purine nucleosides: endogenous neuroprotectants in hypoxic brain.
abstract: 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.
authors.affiliation: Division of Neurobiochemistry, Biocenter Department, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Thauerer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zur Nedden
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baier-Bitterlich
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000473:pathology*; D009416:Nerve Regeneration / Q000187:drug effects; D018696:Neuroprotective Agents; D011684:Purine Nucleosides / Q000494:pharmacology*; D011983:Receptors, Purinergic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D018696:Neuroprotective Agents; D011684:Purine Nucleosides; D011983:Receptors, Purinergic