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Rosiglitazone transiently disturbs calcium homeostasis in monocytic cells

Caddy, J., Singh, N., Atkin, L., Ahluwalia, M., Roberts, A., Lang, Derek, Thomas, A. W. and Webb, R. 2008. Rosiglitazone transiently disturbs calcium homeostasis in monocytic cells. Biochemical and Biophysical Research Communications 366 (1) , pp. 149-155. 10.1016/j.bbrc.2007.11.095

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Abstract

The PPARγ agonist Rosiglitazone exerts anti-hyperglycaemic effects by regulating the long-term expression of genes involved in metabolism, differentiation and inflammation. In the present study, Rosiglitazone treatment rapidly inhibited (5–30 min) the ER Ca2+ ATPase SERCA2b in monocyticcells (IC50 = 1.88 μM; p < 0.05), thereby disrupting short-term Ca2+homeostasis (resting [Ca2+]cyto = 121.2 ± 2.9% basal within 1 h; p < 0.05). However, extended Rosiglitazone treatment (72 h) induced dose-dependent SERCA2b up-regulation, and restored calciumhomeostasis, in monocyticcells (SERCA2b mRNA: 138.7 ± 5.7% basal (1 μM)/215.0 ± 30.9% basal (10 μM); resting [Ca2+]cyto = 97.3 ± 8.3% basal (10 μM)). As unfavourable cardiovascular outcomes, possibly related to disrupted cellular Ca2+homeostasis, have been linked to Rosiglitazone, this effect may be of clinical interest. In contrast, in PPRE-luciferase reporter-gene assays, Rosiglitazone induced non-dose-dependent PPARγ-dependent effects (1 μM: 152.5 ± 4.9% basal; 10 μM: 136.1 ± 5.1% basal (p < 0.05 for 1 μM vs. 10 μM)). Thus, we conclude that Rosiglitazone can exert PPARγ-independent non-genomic effects, such as the SERCA2b inhibition seen here, but that long-term Rosiglitazone treatment did not perturb resting [Ca]cyto in this study.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Rosiglitazone; Monocyte; PPARγ; Intracellular Ca2+; SERCA2b; Anti-hyperglycaemic effects
Publisher: Elsevier
ISSN: 0006-291X
Last Modified: 04 Jun 2017 03:37
URI: http://orca.cf.ac.uk/id/eprint/23835

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