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 |
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: | https://orca.cardiff.ac.uk/id/eprint/23835 |
Citation Data
Cited 7 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
Edit Item |