title: Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats.
abstract: 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.
authors.affiliation: Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana, Cuba.
authors.forename: Javier
authors.initials: J
authors.lastname: Marín-Prida
authors.forename: Nancy
authors.initials: N
authors.lastname: Pavón-Fuentes
authors.forename: Alexey
authors.initials: A
authors.lastname: Llópiz-Arzuaga
authors.forename: Julio R
authors.initials: JR
authors.lastname: Fernández-Massó
authors.forename: Liván
authors.initials: L
authors.lastname: Delgado-Roche
authors.forename: Yssel
authors.initials: Y
authors.lastname: Mendoza-Marí
authors.forename: Seydi Pedroso
authors.initials: SP
authors.lastname: Santana
authors.forename: Alieski
authors.initials: A
authors.lastname: Cruz-Ramírez
authors.forename: Carmen
authors.initials: C
authors.lastname: Valenzuela-Silva
authors.forename: Marcelo
authors.initials: M
authors.lastname: Nazábal-Gálvez
authors.forename: Alberto
authors.initials: A
authors.lastname: Cintado-Benítez
authors.forename: Gilberto L
authors.initials: GL
authors.lastname: Pardo-Andreu
authors.forename: Nadia
authors.initials: N
authors.lastname: Polentarutti
authors.forename: Federica
authors.initials: F
authors.lastname: Riva
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pentón-Arias
authors.forename: Giselle
authors.initials: G
authors.lastname: Pentón-Rol
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004396:Coloring Agents; D016207:Cytokines / Q000096:biosynthesis; D005802:Genes, MHC Class II / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D052980:Phycobilins / Q000302:isolation & purification / Q000494:pharmacology*; D010798:Phycocyanin / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D053545:Spirulina / Q000737:chemistry; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004396:Coloring Agents; D016207:Cytokines; D052980:Phycobilins; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D010798:Phycocyanin; C011069:phycocyanobilin; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; C022616:thiazolyl blue
keywords: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; BCCAo; BSA; C-PC; C-Phycocyanin; CAT; CBF; Cerebral hypoperfusion; DMSO; EAE; GO; Gene Ontology; Gene expression; Inflammation; MDA; MHC-II; MTT; N-methyl-D-aspartate receptors; NMDA-Rs; Oxidative stress; PBS; PC12; PCB; PP; Phycocyanobilin; RAGE; SOD; VEGF; bDC; bilateral common carotid arteries occlusion; bovine serum albumin; brain dendritic cells; catalase; cerebral blood flow; dimethyl sulfoxide; experimental autoimmune encephalomyelitis; major histocompatibility complex class II; malondialdehyde; peroxidation potential; phosphate buffered saline; phycocyanobilin; receptor for advanced glycation end products; recombinant tissue plasminogen activator; rt-PA; superoxide dismutase; vascular endothelial growth factor