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Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress.
J Hypertens. 2012 Feb; 30(2):315-26.JH

Abstract

AIMS

Hypertension is associated with increased plasma inflammatory markers such as cytokines and increased vascular cyclooxygenase-2 (COX-2) expression. The ability of peroxisome proliferator-activated receptor-γ (PPARγ) agonists to reduce oxidative stress seems to contribute to their anti-inflammatory properties. This study analyzes the effect of pioglitazone, a PPARγ agonist, on interleukin-1β-induced COX-2 expression and the role of reactive oxygen species (ROS) on this effect.

METHODS AND RESULTS

Vascular smooth muscle cells from hypertensive rats stimulated with interleukin-1β (10 ng/ml, 24 h) were used. Interleukin-1β increased: 1) COX-2 protein and mRNA levels; 2) protein and mRNA levels of the NADPH oxidase subunit NOX-1, NADPH oxidase activity and ROS production; and 3) phosphorylation of inhibitor of nuclear factor kappa B (IκB) kinase (IKK) nuclear expression of the p65 nuclear factor kappa B (NF-κB) subunit and cell proliferation, all of which were reduced by apocynin (30 μmol/l). Interleukin-1β-induced COX-2 expression was reduced by apocynin, tempol (10 μmol/l), catalase (1000 U/ml) and lactacystin (5 μmol/l). Moreover, H2O2 (50 μmol/l, 90 min) induced COX-2 expression, which was reduced by lactacystin. Pioglitazone (10 μmol/l) reduced the effects of interleukin-1β on: 1) COX-2 protein and mRNA levels; 2) NOX-1 protein and mRNA levels, NADPH oxidase activity and ROS production; and 3) p-IKK, p65 expressions and cell proliferation. Pioglitazone also reduced the H2O2-induced COX-2 expression and increased Cu/Zn and Mn-superoxide dismutase protein expression. PPARγ small interfering RNA (5 nmol/l) further increased interleukin-1β-induced COX-2 and NOX-1 mRNA levels. In addition, pioglitazone increased the interleukin-1β-induced PPARγ mRNA levels.

CONCLUSION

PPARγ activation with pioglitazone reduces interleukin-1β-induced COX-2 expression by interference with the redox-sensitive transcription factor NF-κB.

Authors+Show Affiliations

Departamento de Bioquímica, Fisiología y Genética Molecular, Universidad Rey Juan Carlos, Alcorcón, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22179086

Citation

Martín, Angela, et al. "Peroxisome Proliferator-activated Receptor-γ Activation Reduces Cyclooxygenase-2 Expression in Vascular Smooth Muscle Cells From Hypertensive Rats By Interfering With Oxidative Stress." Journal of Hypertension, vol. 30, no. 2, 2012, pp. 315-26.
Martín A, Pérez-Girón JV, Hernanz R, et al. Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress. J Hypertens. 2012;30(2):315-26.
Martín, A., Pérez-Girón, J. V., Hernanz, R., Palacios, R., Briones, A. M., Fortuño, A., Zalba, G., Salaices, M., & Alonso, M. J. (2012). Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress. Journal of Hypertension, 30(2), 315-26. https://doi.org/10.1097/HJH.0b013e32834f043b
Martín A, et al. Peroxisome Proliferator-activated Receptor-γ Activation Reduces Cyclooxygenase-2 Expression in Vascular Smooth Muscle Cells From Hypertensive Rats By Interfering With Oxidative Stress. J Hypertens. 2012;30(2):315-26. PubMed PMID: 22179086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress. AU - Martín,Angela, AU - Pérez-Girón,José V, AU - Hernanz,Raquel, AU - Palacios,Roberto, AU - Briones,Ana M, AU - Fortuño,Ana, AU - Zalba,Guillermo, AU - Salaices,Mercedes, AU - Alonso,María J, PY - 2011/12/20/entrez PY - 2011/12/20/pubmed PY - 2012/5/9/medline SP - 315 EP - 26 JF - Journal of hypertension JO - J Hypertens VL - 30 IS - 2 N2 - AIMS: Hypertension is associated with increased plasma inflammatory markers such as cytokines and increased vascular cyclooxygenase-2 (COX-2) expression. The ability of peroxisome proliferator-activated receptor-γ (PPARγ) agonists to reduce oxidative stress seems to contribute to their anti-inflammatory properties. This study analyzes the effect of pioglitazone, a PPARγ agonist, on interleukin-1β-induced COX-2 expression and the role of reactive oxygen species (ROS) on this effect. METHODS AND RESULTS: Vascular smooth muscle cells from hypertensive rats stimulated with interleukin-1β (10 ng/ml, 24 h) were used. Interleukin-1β increased: 1) COX-2 protein and mRNA levels; 2) protein and mRNA levels of the NADPH oxidase subunit NOX-1, NADPH oxidase activity and ROS production; and 3) phosphorylation of inhibitor of nuclear factor kappa B (IκB) kinase (IKK) nuclear expression of the p65 nuclear factor kappa B (NF-κB) subunit and cell proliferation, all of which were reduced by apocynin (30 μmol/l). Interleukin-1β-induced COX-2 expression was reduced by apocynin, tempol (10 μmol/l), catalase (1000 U/ml) and lactacystin (5 μmol/l). Moreover, H2O2 (50 μmol/l, 90 min) induced COX-2 expression, which was reduced by lactacystin. Pioglitazone (10 μmol/l) reduced the effects of interleukin-1β on: 1) COX-2 protein and mRNA levels; 2) NOX-1 protein and mRNA levels, NADPH oxidase activity and ROS production; and 3) p-IKK, p65 expressions and cell proliferation. Pioglitazone also reduced the H2O2-induced COX-2 expression and increased Cu/Zn and Mn-superoxide dismutase protein expression. PPARγ small interfering RNA (5 nmol/l) further increased interleukin-1β-induced COX-2 and NOX-1 mRNA levels. In addition, pioglitazone increased the interleukin-1β-induced PPARγ mRNA levels. CONCLUSION: PPARγ activation with pioglitazone reduces interleukin-1β-induced COX-2 expression by interference with the redox-sensitive transcription factor NF-κB. SN - 1473-5598 UR - https://www.unboundmedicine.com/medline/citation/22179086/Peroxisome_proliferator_activated_receptor_γ_activation_reduces_cyclooxygenase_2_expression_in_vascular_smooth_muscle_cells_from_hypertensive_rats_by_interfering_with_oxidative_stress_ L2 - https://doi.org/10.1097/HJH.0b013e32834f043b DB - PRIME DP - Unbound Medicine ER -