Effect of CRH on NO bioavailability, ROS production and antioxidant defense systems in endothelial EAhy926 cells.
Local or 'Immune' Corticotropin-Releasing Hormone (CRH) is secreted in peripheral tissues and plays a direct immunomodulatory role as an endocrine or paracrine mediator of inflammation. The present study was undertaken to determine whether CRH affects the endothelial redox state. Accordingly, intracellular reactive oxygen species (ROS) content and peroxynitrite levels, endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels as well as catalase activity, superoxide dismutase (SOD) activity and glutathione (GSH) levels were measured in the presence or absence of selective CRH receptor-1 and CRH receptor-2 inhibitors in endothelial EAhy926 cells exposed in vitro in 10(-7) M CRH for 2 h. CRH acting through both receptors induced a significant increase of ROS content (p < 0.001), catalase activity (p < 0.001) and SOD activity (p < 0.001), accompanied by a simultaneous significant decrease of eNOS activity and NO levels (p < 0.001), as well as a significant increase in nitrotyrosine (peroxynitrite) levels (p < 0.05). The data indicate that CRH may act as a regulator of pro-inflammatory mechanisms inducing adaptation of endothelial cell function to local stress.
Department of Endocrinology and Metabolic Diseases, Larissa University Hospital, Greece.
Sofia
S
Gougoura
Panagiotis
P
Liakos
George N
GN
Koukoulis
D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000493:pharmacokinetics*; D017077:Culture Media, Conditioned / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D006801:Humans; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D000099052:CRF Receptor, Type 1
D000975:Antioxidants; C101531:CRF receptor type 2; D017077:Culture Media, Conditioned; D009566:Nitrates; D009573:Nitrites; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011743:Pyrimidines; D011758:Pyrroles; D017382:Reactive Oxygen Species; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; C528574:astressin-2B; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D002374:Catalase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D005978:Glutathione