Aich, Jyotirmoi ; Mabalirajan, Ulaganathan ; Ahmad, Tanveer ; Khanna, Kritika ; Rehman, Rakshinda ; Agrawal, Anurag ; Ghosh, Balaram (2012) Resveratrol attenuates experimental allergic asthma in mice by restoring inositol polyphosphate 4 phosphatase (INPP4A) International Immunopharmacology, 14 (4). pp. 438-443. ISSN 1567-5769
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Official URL: http://doi.org/10.1016/j.intimp.2012.08.017
Related URL: http://dx.doi.org/10.1016/j.intimp.2012.08.017
Abstract
Asthma is a chronic airway inflammatory disorder which is characterized by reversible airway obstruction, airway hyperresponsiveness and airway inflammation. Oxidative stress has been shown to be strongly associated with most of the features of asthma and leads to accumulation of phosphatidyl inositol (3,4) bis-phosphate {PtdIns(3,4)P2} which is the major substrate for inositol polyphosphate 4 phosphatase (INPP4A). PtdIns(3,4)P2 in turn activates PI3K pathway and contributes to oxidative stress. Thus, there exists a vicious loop between oxidative stress and lipid phosphatase signaling. In this context, we have recently shown that INPP4A, a crucial molecular checkpoint in controlling PI3K-Akt signaling pathway, is downregulated in allergic airway inflammation. Resveratrol, a potent antioxidant found in red wines, has been shown to attenuate asthma features in murine model of allergic airway inflammation (AAI), however the underlying mode of its action was not completely understood. In this study, the effect of resveratrol on mitochondrial dysfunction, PI3K-Akt signaling and inositol polyphosphate 4 phosphatase was studied in murine model of allergic airway inflammation. We observed that resveratrol treatment of allergic mice was found to significantly downregulate oxidative stress and restore mitochondrial function. It also decreased calpain activity and restored the expression of INPP4A in lungs which in turn reduced Akt kinase activity and Akt phosphorylation. These results suggest a novel mechanism of action of resveratrol in attenuating asthma phenotype by downregulating PI3K-Akt pathway via upregulating INPP4A.
Item Type: | Article |
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Source: | Copyright of this article belongs to Elsevier Science. |
Keywords: | Inositol Polyphosphate 4 Phosphatase (INPP4A); Resveratrol; Asthma; AHR; PI3K-Akt; Mitochondrial Dysfunction. |
ID Code: | 120999 |
Deposited On: | 08 Jul 2021 07:56 |
Last Modified: | 08 Jul 2021 07:56 |
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