Healthy ageing and depletion of intracellular glutathione influences T cell membrane thioredoxin-1 levels and cytokine secretion

Background: During ageing an altered redox balance has been observed in both intracellular and extracellular compartments, primarily due to glutathione depletion and metabolic stress. Maintaining redox homeostasis is important for controlling proliferation and apoptosis in response to specific stimuli for a variety of cells. For T cells, the ability to generate specific response to antigen is dependent on the oxidation state of cell surface and cytoplasmic protein-thiols. Intracellular thiols are maintained in their reduced state by a network of redox regulating peptides, proteins and enzymes such as glutathione, thioredoxins and thioredoxin reductase. Here we have investigated whether any relationship exists between age and secreted or cell surface thioredoxin-1, intracellular glutathione concentration and T cell surface thioredoxin 1 (Trx-1) and how this is related to interleukin (IL)-2 production.Results: Healthy older adults have reduced lymphocyte surface expression and lower circulating plasma Trx-1 concentrations. Using buthionine sulfoximine to deplete intracellular glutathione in Jurkat T cells we show that cell surface Trx-1 is lowered, secretion of Trx-1 is decreased and the response to the lectin phytohaemagglutinin measured as IL-2 production is also affected. These effects are recapitulated by another glutathione depleting agent, diethylmaleate.Conclusion: Together these data suggest that a relationship exists between the intracellular redox compartment and Trx-1 proteins. Loss of lymphocyte surface Trx-1 may be a useful biomarker of healthy ageing. © 2013 Carilho Torrao et al.; licensee Chemistry Central Ltd

GIT2 Acts as a Potential Keystone Protein in Functional Hypothalamic Networks Associated with Age-Related Phenotypic Changes in Rats

The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process

Seeing is believing? The role of aesthetics in assessing religion cross-culturally

The opinion that Japanese religion was rather “spiritual” or “superstitious” has, albeit being reproached for its Eurocentric basis, reached noteworthy spread and tempted scientific explanations. Yet, aside from dogmatic or structural differences to monotheistic religions, a major reason for the aforementioned impression may be that experiencing religion in Japan mismatches the religious experience familiar to the non-Japanese observer. This personal, immediate, aesthetic experience has been excluded from argumentation for its subjective inclination. It is argued, though, that our judgment always settles between discursive knowledge and aesthetic experience, both influencing each other.This paper will trace the inversion of the discourse on Japanese religion from Ōnishi Hajime’s diagnosis that Japanese religious tradition was insufficient for the establishment of national art, up to Richard B. Pilgrim’s claim of a ‘religio-aesthetic tradition of Japan’. It is then argued that this gradual acknowledgement of the aesthetic dimension in religious experience can be beneficial for cross-cultural understanding since it provides access for religious outsiders and since aesthetic subjectivity can itself become a basis for objective statements if it is recognized as inevitable basis for descriptive categories

Kulturbegegnung als Bildbegegnung: Zum hermeneutischen Potential der Bilder vom Anderen

Die Ästhetisierung als ‚ausklammerndes‘ Sehen anderer Kulturen hat in der Vergangenheit eine negative Konnotation erfahren, weil ihr das Produzieren stereotyper Bilder und eine konstitutive Rolle in Orientalismus und Kolonialismus zugeschrieben wurden. Demgegenüber sind positive Wirkungen einer Ästhetisierung als ‚Vereigentlichung‘ des Angeschauten vorgebracht worden. In beiden Fällen steht Ästhetisierung unter dem Verdacht, ein einbahniges Verstehen zu unterstützen, das Sehgewohnheiten unhinterfragt ließ. Um eine Lesart vorzuschlagen, bei der das Sehen als ein wechselseitiges thematisiert wird, soll diese Problemstellung am Beispiel des Anschauens von Bildern des Anderen untersucht werden. Dabei wird angenommen, dass der Ästhetisierung bisher ein konzeptuelles Bild zugrunde liegt, welches eine unvoreingenommene sinnliche Erkenntnis hemmt. Hier hingegen werden die hermeneutischen Potentiale eines Bildsehens aus interkultureller Perspektive diskutiert. Es wird vorgeschlagen, wie sich das Konzept ‚Bild‘ ändern könnte, um den Bildern anderer Kulturen möglichst erkenntnisoffen zu begegnen. Ästhetisierung wird in diesem Sinne als produktive Option der interkulturellen Begegnung in Aussicht gestellt

Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of alpha 1- and alpha 2-adrenoceptor activation

The contractile effect of norepinephrine (NE) on isolated rabbit bronchial artery rings (150-300 microns in diameter) and the role of alpha 1- and alpha 2-adrenoceptors (AR) on smooth muscle and endothelium were studied. In intact arteries, NE increased tension in a dose-dependent manner, and the sensitivity for NE was further increased in the absence of endothelium. In intact but not in endothelium-denuded arteries, the response to NE was increased in the presence of both indomethacin (Indo; cyclooxygenase inhibitor) and NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthase inhibitor], indicating that two endothelium-derived factors, NO and a prostanoid, modulate the NE-induced contraction. The alpha 1-AR antagonist prazosin shifted the NE dose-response curve to the right, and phenylephrine (alpha 1-AR agonist) induced a dose-dependent contraction that was potentiated by L-NAME or removal of the endothelium. The sensitivity to NE was increased slightly by the alpha 2-AR antagonists yohimbine and idazoxan, and this effect was abolished by Indo or removal of the endothelium. Similarly, contractions induced by UK-14304 (alpha 2-AR agonist) were potentiated by Indo or removal of the endothelium. These results suggest that NE-induced contraction is mediated through activation of alpha 1- and alpha 2-ARs on both smooth muscle and endothelium. Activation of the alpha 1- and alpha 2-ARs on the smooth muscle causes contraction, whereas activation of the endothelial alpha 1- and alpha 2-ARs induces relaxation through release of NO (alpha 1-ARs) and a prostanoid (alpha 2-ARs)