Induction of hemeoxygenase-1 expression after inhibition of hemeoxygenase activity promotes inflammation and worsens ischemic brain damage in mice

• Published in: Neuroscience Vol. 243; pp. 22 - 32
• Main Authors: Pérez-de-Puig, I, Martín, A, Gorina, R, de la Rosa, X, Martinez, E, Planas, A.M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 23.07.2013; Elsevier
• Subjects: Animals; Bach-1; Basic-Leucine Zipper Transcription Factors - biosynthesis; Biological and medical sciences; Blotting, Western; brain damage; Brain Ischemia - enzymology; Brain Ischemia - genetics; Brain Ischemia - pathology; Enzyme Inhibitors - pharmacology; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; hemeoxygenase (HO); HO-1; Inflammation - enzymology; Inflammation - genetics; Male; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Neurology; Protoporphyrins - pharmacology; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; stroke; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; NADPH; TTC; HO; hemeoxygenase (HO); heat-shock protein; ICAM-1; HO-1; BRCA1; phosphate-buffered saline; Bach-1; analysis of variance; ANOVA; Nrf2; hemeoxigenase; BRCA1-associated C-terminal helicase1; Glut-1; interleukin; HPLC; intercellular adhesion molecule-1; PBS; antioxidant-responsive element; IL; HSP; zinc proto-porphyrin IX; nicotinamide adenine dinucleotide phosphate; qRT-PCR; MCA; triphenyltetrazolium chloride; brain damage; high-performance liquid chomatography; quantitative real-time reverse transcription polymerase chain reaction; stroke; middle cerebral artery; breast cancer type 1 susceptibility protein; bZIP; VCAM-1; ARE; TNF-α; basic region/leucine zipper motif; tumor necrosis factor-α; vascular cell adhesion protein-1; pMCAO; glucose transporter-1; permanent middle cerebral artery occlusion; GAPDH; nuclear factor erythroid 2-related factor 2; ZnPP; glyceraldehyde 3-phosphate dehydrogenase; Nervous system diseases; Stroke; Rodentia; Central nervous system; Cardiovascular disease; Inflammation; Cerebral disorder; Encephalon; Vascular disease; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Cerebrovascular disease
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2013.03.046

Highlights • Ischemia down-modulates HO-1 gene repressor Bach-1 and induces HO-1 expression. • HO inhibitor ZnPP induces HO-1 in brain vessels 24 h after systemic administration. • Treatment with ZnPP 24 h before ischemia exacerbates inflammation and brain damage. • Treatment with ZnPP 30 min before ischemia does not increase infarct volume. • A detrimental action of HO-1 in the absence of HO activity is proposed.