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May D Baastrup J Nientit MR Binder A Schünke M Baron R Cascorbi I 《The Journal of biological chemistry》2012,287(32):27087-27094
The role of genetic modifications of the TRPA1 receptor has been well documented in inflammatory and neuropathic pain. We recently reported that the E179K variant of TRPA1 appears to be crucial for the generation of paradoxical heat sensation in pain patients. Here, we describe the consequences of the single amino acid exchange at position 179 in the ankyrin repeat 4 of human TRPA1. TRPA1 wild type Lys-179 protein expressed in HEK cells exhibited intact biochemical properties, inclusive trafficking into the plasma membrane, formation of large protein complexes, and the ability to be activated by cold. Additionally, a strong increase of Lys-179 protein expression was observed in cold (4 °C) and heat (49 °C)-treated cells. In contrast, HEK cells expressing the variant Lys-179 TRPA1 failed to get activated by cold possibly due to the loss of ability to interact with other proteins or other TRPA1 monomers during oligomerization. In conclusion, the detailed understanding of TRPA1 genetic variants might provide a fruitful strategy for future development of pain treatments. 相似文献
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Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway 总被引:3,自引:0,他引:3
Weiser Martin R.; Pechet Taine T.V.; Williams Julian P.; Ma Minghe; Frenette Paul S.; Moore Francis D.; Kobzik Lester; Hines Richard O.; Wagner Denisa D.; Carroll Michael C.; Hechtman Herbert B. 《Journal of applied physiology》1997,83(4):1090-1095
Weiser, Martin R., Taine T. V. Pechet, Julian P. Williams,Minghe Ma, Paul S. Frenette, Francis D. Moore, Lester Kobzik, RichardO. Hines, Denisa D. Wagner, Michael C. Carroll, and Herbert B. Hechtman. Experimental murine acid aspiration injury is mediatedby neutrophils and the alternative complement pathway. J. Appl. Physiol. 83(4):1090-1095, 1997.Acid aspiration may result in the development ofthe acute respiratory distress syndrome, an event associated withsignificant morbidity and mortality. Although once attributed to directdistal airway injury, the pulmonary failure after acid aspiration ismore complex and involves an inflammatory injury mediated by complement(C) and polymorphonuclear leukocytes. This study examines the injuriousinflammatory cascades that are activated after acid aspiration. Therole of neutrophils was defined by immunodepletion before aspiration,which reduced injury by 59%. The injury was not modified in either P-or E-selectin-knockout mice, indicating that these adhesion moleculeswere not operative. C activation after aspiration was documented withimmunochemistry by C3 deposition on injured alveolar pneumocytes.Animals in which C activation was inhibited with soluble C receptortype 1 (sCR1) had a 54% reduction in injury, similar to the level ofprotection seen in C3-knockout mice (58%). However C4-knockout micewere not protected from injury, indicating that C activation ismediated by the alternative pathway. Finally, an additive effect ofneutrophils and C was demonstrated whereby neutropenic animals thatwere treated with sCR1 showed an 85% reduction in injury. Thus acidaspiration injury is mediated by neutrophils and the alternative Cpathway. 相似文献
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Background
According to recent clinical findings epileptiform activity in temporolimbic structures may cause depressive and other psychiatric symptoms that may occur independently of any seizure in patient''s history. In addition in these patients subclinical seizure-like activity with indirect clinical manifestations likely may occur in a form of various forms of cognitive, affective, memory, sensory, behavioral and somatic symptoms (the so-called complex partial seizure-like symptoms). A typical characteristic of epileptiform changes is increased neural synchrony related to spreading of epileptiform activity between hemispheres even in subclinical conditions i.e. without seizures. These findings suggest a hypothesis that measures reflecting a level of synchronization and information transfer between hemispheres could reflect spreading of epileptiform activity and might be related to complex partial seizure-like symptoms.Methods and Findings
Suitable data for such analysis may provide various physiological signals reflecting brain laterality, as for example bilateral electrodermal activity (EDA) that is closely related to limbic modulation influences. With this purpose we have performed measurement and analysis of bilateral EDA and compared the results with psychometric measures of complex partial seizure-like symptoms, depression and actually experienced stress in 44 patients with unipolar depression and 35 healthy controls. The results in unipolar depressive patients show that during rest conditions the patients with higher level of complex partial seizure like symptoms (CPSI) display increased level of EDA transinformation (PTI) calculated between left and right EDA records (Spearman correlation between CPSI and PTI is r = 0.43, p = 0.004).Conclusions
The result may present potentially useful clinical finding suggesting that increased EDA transinformation (PTI) could indirectly indicate increased neural synchrony as a possible indicator of epileptiform activity in unipolar depressive patients treated by serotoninergic antidepresants. 相似文献68.
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