Immunosuppressant cytoprotection correlates with HMGB1 suppression in primary astrocyte cultures exposed to combined oxygen-glucose deprivation.
Journal Title: Pharmacological Reports - Year 2011, Vol 63, Issue 2
Abstract
The protective potential of immunosuppressants has been reported in many experimental models of ischemia both in vivo and in vitro, suggesting a novel therapeutic application of these drugs. Because high-mobility group box 1 (HMGB1) protein has recently been reported to be involved in ischemic brain injury, the purpose of the present study was to determine whether treatment with immunosuppressants could decrease the expression and release of HMGB1 in astrocytes exposed to simulated ischemic conditions (combined oxygen-glucose deprivation, OGD). We also investigated whether immunosuppressive drugs could attenuate necrosis in astrocyte cultures exposed to OGD. Finally, we studied the influence of immunosuppressants on the expression of NFκB, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Cells were treated with cyclosporine A, FK506 and rapamycin (all drugs at concentrations of 0.1, 1 and 10 μM). Our study provides evidence that immunosuppressants decrease the expression and release of HMGB1 in ischemic astrocytes. Our data suggest that HMGB1 release may be partly an active process triggered by oxidative stress because the antioxidant N-acetylcysteine (NAC) clearly attenuated HMGB1 expression and release. Furthermore, we show that the immunosuppressants, at the same concentrations that significantly suppressed HMGB1 expression and release, were also able to prevent the necrosis of ischemic astrocytes and inhibit the expression of inflammatory mediators (NFκ, iNOS and COX-2). These results provide further information about the cytoprotective mechanisms of immunosuppressants on ischemic astrocytes, especially in relation to the pathophysiology of ischemic brain injury. It appears that the protective effects of immunosuppressants can be mediated in part by the suppressing the expression and release of HMGB1 in astrocytes, which leads to the attenuation of ischemia-induced necrosis and neuroinflammation.
Authors and Affiliations
Bożena Gabryel, Anna Bielecka, Jacek Bernacki, Krzysztof Łabuzek, Zbigniew Herman
Keywords
Related Articles
- EP ID EP139924
- DOI -
- Views 67
- Downloads 0
Magnesium in depression.
Magnesium is one of the most essential mineral in the human body, connected with brain biochemistry and the fluidity of neuronal membrane. A variety of neuromuscular and psychiatric symptoms, including different types of...
Novel approaches to improving endothelium-dependent nitric oxide-mediated vasodilatation.
Endothelial dysfunction, which is defined by decreased endothelium-dependent vasodilatation, is associated with an increased number of cardiovascular events. Nitric oxide (NO) bioavailability is reduced by altered endoth...
Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis.
Background: In addition to recognized antimalarial effects, Artemisia annua L. (Qinghao) possesses anticancer properties. The underlying mechanisms of this activity are unknown. The aim of our experiments was to investig...
Zinc and depression. An update.
Unsatisfactory clinical efficacy and a variety of adverse effects of current antidepressant drugs have incited search for better therapy. Zinc, an antagonist of the glutamate/N-methyl-D-aspartate (NMDA) receptor, exhibit...
Functional effects of polyamines via activation of human β1- and β2-adrenoceptors stably expressed in CHO cells.
Polyamines mediate acute metabolic effects and cardiac hypertrophy associated with β-adrenoceptor stimulation. They may also modulate β-adrenoceptors, causing functional responses in rat atria and tracheal smooth muscle....