Neurochemistry international, 2011-11, Vol.59 (6), p.739-748
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Mitochondrial ERK plays a key role in delta-opioid receptor neuroprotection against acute mitochondrial dysfunction
- Ist Teil von
- Neurochemistry international, 2011-11, Vol.59 (6), p.739-748
- Ort / Verlag
- Kidlington: Elsevier Ltd
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- ► DOR stimulation attenuates NaN 3-induced acute neuronal mitochondrial dysfunction. ► DOR activation suppresses neuronal injury caused by acute NaN 3 insults. ► DOR activation protects neurons from acute NaN 3 insults mainly via PKC–ERK pathway. ► Mitochondrial ERK is required for DOR protection against mitochondrial dysfunction. It is well established that stimulating delta-opioid receptor (DOR) with its specific agonists elicits neuroprotection against hypoxia/ischemia. Mitochondrial dysfunction plays a key role in hypoxic neuronal injury, but the effects of DOR activation on mitochondrial dysfunction in neurons are poorly elucidated. In this investigation, we studied the effects of [ d-Ala2, d-Leu5] enkephalin (DADLE), a potent DOR agonist, on acute mitochondrial dysfunction and ensuing cell damage induced by sodium azide in primary rat cortical neuronal cultures, and explored possible mechanisms underlying. Here, we show that DADLE reverses NaN 3-induced acute mitochondrial dysfunction by selectively activating DOR, mainly including mitochondrial membrane depolarization, mitochondrial Ca 2+ overload and reactive oxygen species generation. DOR stimulation also inhibits cytochrome c release and caspase-3 activation, and attenuates neuronal death caused by acute NaN 3 insults. Furthermore, DOR activation with DADLE protects neurons from acute NaN 3 insults mainly through PKC–ERK pathway, and mitochondrial ERK activation is especially required for DOR neuroprotection against acute mitochondrial dysfunction.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0197-0186eISSN: 1872-9754DOI: 10.1016/j.neuint.2011.08.005Titel-ID: cdi_proquest_miscellaneous_902378179
- Format
- –
- Schlagworte
- Acute Disease, Acute mitochondrial dysfunction, Analgesics, Opioid - pharmacology, Animals, Biological and medical sciences, Cytoprotection - drug effects, Cytoprotection - physiology, Delta-opioid receptor, Enkephalin, Leucine-2-Alanine - pharmacology, Enzyme Activation - drug effects, Enzyme Activation - physiology, Fundamental and applied biological sciences. Psychology, Mitochondrial Diseases - drug therapy, Mitochondrial Diseases - enzymology, Mitochondrial Diseases - metabolism, Mitogen-Activated Protein Kinase 3 - physiology, Mitogen-activated protein kinases, Neurons - drug effects, Neurons - enzymology, Neurons - metabolism, Neuroprotection, p38 Mitogen-Activated Protein Kinases - physiology, Primary Cell Culture, Primary rat cortical neuron cultures, Rats, Rats, Sprague-Dawley, Receptors, Opioid, delta - agonists, Receptors, Opioid, delta - physiology, Sodium azide, Sodium Azide - toxicity, Vertebrates: nervous system and sense organs