Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

• Published in: Toxicology and applied pharmacology 2013-10, Vol.272 (1), p.49-60
• Main Authors: Marín-Prida, Javier, Pavón-Fuentes, Nancy, Llópiz-Arzuaga, Alexey, Fernández-Massó, Julio R., Delgado-Roche, Liván, Mendoza-Marí, Yssel, Santana, Seydi Pedroso, Cruz-Ramírez, Alieski, Valenzuela-Silva, Carmen, Nazábal-Gálvez, Marcelo, Cintado-Benítez, Alberto, Pardo-Andreu, Gilberto L., Polentarutti, Nadia, Riva, Federica, Pentón-Arias, Eduardo, Pentón-Rol, Giselle
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Biological and medical sciences; Biomarkers - metabolism; BRAIN; Brain Chemistry - drug effects; Brain Chemistry - genetics; CAROTID ARTERIES; CATALASE; CATTLE; Cell Survival - drug effects; Cerebral hypoperfusion; Cerebrovascular Disorders - drug therapy; Cerebrovascular Disorders - physiopathology; Coloring Agents; Cytokines - biosynthesis; Gene expression; GENES; Genes, MHC Class II - drug effects; Glutamic Acid - metabolism; HISTOCOMPATIBILITY COMPLEX; Hydrogen Peroxide - pharmacology; INFLAMMATION; Inflammation - genetics; Male; Medical sciences; Microarray Analysis; Neurology; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; PC12; PC12 Cells; Phycobilins - isolation & purification; Phycobilins - pharmacology; PHYCOCYANIN; Phycocyanin - isolation & purification; Phycocyanin - pharmacology; Phycocyanobilin; POLYCHLORINATED BIPHENYLS; RATS; Rats, Wistar; Real-Time Polymerase Chain Reaction; RECEPTORS; Spirulina - chemistry; STRESSES; Tetrazolium Salts; Thiazoles; Vascular diseases and vascular malformations of the nervous system; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2013.05.021

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. [Display omitted] •Phycocyanobilin (PCB) prevents H2O2 and glutamate induced PC12 cell viability loss.•Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH).•PCB modulates 190 genes associated to inflammation in acute CH.•PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment.•PCB restores redox and immune balances showing promise as potential stroke therapy.