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| Content Provider | Springer Nature Link |
|---|---|
| Author | Chistyakov, D. V. Popova, N. V. Grabeklis, S. A. Aleshin, S. E. Sergeeva, M. G. |
| Copyright Year | 2012 |
| Abstract | Epidemiological studies have shown that severe inflammatory responses occur in patients with hyperglycemia. The molecular nature of these changes is currently under intense investigations. A central role of nuclear receptors PPAR has been shown in the regulation of metabolic changes associated with hyperglycemia, a selective agonist of nuclear receptor PPARγ rosiglitazone is used as a hypoglycemic drug. Rosiglitazone is known to have anti-inflammatory effects, but its properties as an anti-inflammatory drug in hyperglycemic conditions have not been studied. This was an aim of our work. We used a human cell culture model of hyperglycemia: HeLa cells incubated in the conditions of 25 mM glucose for 3 days. Control cells were incubated with 5 mM glucose. The cells were stimulated with lipopolysaccharide (LPS) that is known to trigger innate immune response through activation of Toll-like receptor 4 and influence mRNA expression levels of three of PPAR (α, β/δ, γ) isotypes as well as cyclooxygenase (COX-1 and COX-2). We have shown that under hyperglycemic conditions expression levels of PPARα and PPARβ/δ decreased almost twofold, expression level of COX-2 also decreased, while expression levels of COX-1 and PPARγ remained unchanged compared to those under normal glucose concentration. LPS administration in control cells leads to a 1.5–2.5-fold stimulation of expression of COX-2 and PPAR isotypes. In contrast, under hyperglycemia, LPS exhibited no effect on expression of COX-2 and the PPAR isotypes, which indicates potential mechanisms of hyperglycemia-related alterations in innate immunity. Rosiglitazone, an agonist of PPARγ, decreased expression level of PPARβ/δ and abolished the effect of LPS under hyperglycemia. Rosiglitazone also reduced expression level of COX-1 and COX-2, which indicates on the agonist possible role as an anti-inflammatory agent under high glucose concentrations. These data broaden applicability of rosiglitazone as an anti-inflammatory agent in hyperglycemic conditions. |
| Starting Page | 75 |
| Ending Page | 81 |
| Page Count | 7 |
| File Format | |
| ISSN | 19907478 |
| Journal | Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology |
| Volume Number | 6 |
| Issue Number | 1 |
| e-ISSN | 19907494 |
| Language | English |
| Publisher | SP MAIK Nauka/Interperiodica |
| Publisher Date | 2012-02-25 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | nuclear receptors hyperglycemia inflammation cyclooxygenase gene expression Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Biophysics |
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