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

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 24 h 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 H{sub 2}O{sub 2} 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 whichmore » further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} 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.« less
Authors:
 [1] ;  [2] ; ;  [3] ;  [1] ; ; ; ; ; ;  [3] ;  [1] ;  [4] ;  [5] ;  [3] ;  [3]
  1. 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)
  2. International Centre for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, PO Box: 11300, Havana (Cuba)
  3. Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba)
  4. Istituto Clinico Humanitas (IRCCS), Rozzano (Italy)
  5. Department of Veterinary Science and Public Health (DIVET), University of Milano (Italy)
Publication Date:
OSTI Identifier:
22285394
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 272; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRAIN; CAROTID ARTERIES; CATALASE; CATTLE; GENES; HISTOCOMPATIBILITY COMPLEX; INFLAMMATION; PHYCOCYANIN; POLYCHLORINATED BIPHENYLS; RATS; RECEPTORS; STRESSES