Journal of neurochemistry
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Journal of neurochemistry · Oct 2008
Pre-conditioning induced by carbon monoxide provides neuronal protection against apoptosis.
Carbon monoxide (CO) is an endogenous product of mammalian cells generated by heme-oxygenase, presenting anti-apoptotic properties in several tissues. The present work demonstrates the ability of small amounts of exogenous CO to prevent neuronal apoptosis induced by excitotoxicity and oxidative stress in mice primary culture of cerebellar granule cells. Additionally, our data show that endogenous CO is a heme-oxygenase product critical for its anti-apoptotic activity. ⋯ Opening of mitoK(ATP), which appears to be critical for CO prevention of apoptosis, might be a later event. We also demonstrated that reactive oxygen species generation and de novo protein synthesis are necessary for CO PC effect and neuroprotection. In conclusion, CO induces PC and prevents neuronal apoptosis, therefore constituting a novel and promising candidate for neuroprotective therapies.
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Journal of neurochemistry · Oct 2008
Characterization of urotensin II, distribution of urotensin II, urotensin II-related peptide and UT receptor mRNAs in mouse: evidence of urotensin II at the neuromuscular junction.
Urotensin II (UII) and UII-related peptide (URP) are paralog neuropeptides whose existence and distribution in mouse have not yet been investigated. In this study, we showed by HPLC/RIA analysis that the UII-immunoreactive molecule in the mouse brain corresponds to a new UII(17) isoform. Moreover, calcium mobilization assays indicated that UII(17) and URP were equally potent in stimulating UII receptor (UT receptor). ⋯ By contrast, the UT receptor mRNA was widely expressed, and notably, very high amounts of transcript occurred in skeletal muscle and prostate. In the biceps femoris muscle, UII-like immunoreactivity was shown to coexist with synaptophysin in muscle motor end plate regions. Altogether these results suggest that (i) UII and URP may have many redundant biological effects, especially at the neuromuscular junction; (ii) URP may more specifically participate to autonomic, cardiovascular and reproductive functions.
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Journal of neurochemistry · Oct 2008
JAK/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat.
Peripheral nerve lesion leads to the production of interleukin 6 (IL-6)-related neuropoietic cytokines involved in nerve protection and regeneration. This family of cytokines mainly signal through the signal transducer and activator of transcription (STAT) pathway that is locally activated in injured nerves. IL-6 is also involved in pain that frequently arises from peripheral nerve lesion. ⋯ Intrathecal injection of anti-rat IL-6 antibodies prevented the SNL-induced accumulation of phospho-STAT3 in the spinal cord. STAT3 pathway blockade with Janus kinase 2 inhibitor AG490 attenuated both mechanical allodynia and thermal hyperalgesia in SNL rats. These data show that in response to SNL injury Janus kinase/STAT3 system is activated mainly through IL-6 signaling in spinal microglia and that this transduction pathway participates in development of pain associated with nerve alteration.
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Journal of neurochemistry · Oct 2008
Genistein, a natural phytoestrogen from soy, relieves neuropathic pain following chronic constriction sciatic nerve injury in mice: anti-inflammatory and antioxidant activity.
There is great interest in soy isoflavones as alternatives to endogenous estrogens not only in hormonal pathologies, but also in inflammatory, neurodegenerative diseases, and pain. We investigated the effect of the isoflavone genistein on neuropathic pain. Genistein binds estrogen receptors (ER) with higher affinity for the ERbeta particularly expressed in neuronal and immune cells. ⋯ Antioxidant effects are also involved as the anti-nociceptive dose reversed the increase in reactive oxygen species and malondialdehyde in injured paw tissues, and increased the activity of anti-oxidant enzymes. The phytoestrogen had immunomodulatory and anti-inflammatory activities as it reduced peripheral and central nuclear factor-kappaB, nitric oxide system and pro-inflammatory cytokine over-activation. Taken together, our results suggest that genistein could ameliorate painful neuropathy by multiple mechanisms.