Osteopontin expression during early cerebral ischemia-reperfusion in rats: enhanced expression in the right cortex is suppressed by acetaminophen

• Published in: PloS one 2011-01, Vol.6 (1), p.e14568
• Main Authors: Baliga, Sunanda S, Merrill, Gary F, Shinohara, Mari L, Denhardt, David T
• Format: Article
• Language: English
• Subjects: Acetaminophen; Acetaminophen - pharmacology; Animals; Apoptosis; Biocompatibility; Brain; Brain Ischemia - metabolism; Caspase; Caspase-9; Cell Biology/Cellular Death and Stress Responses; Cellular signal transduction; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cytoplasm; Extracellular matrix; Forebrain; Gene Expression - drug effects; Infiltration; Inflammation; Injuries; Ischemia; Macrophages; Mitochondria; Neuroscience/Neural Homeostasis; Neuroscience/Neurobiology of Disease and Regeneration; Neurosciences; Nitric oxide; Osteopontin; Osteopontin - analysis; Osteopontin - biosynthesis; Osteopontin - drug effects; Rats; Reperfusion; Reperfusion Injury - metabolism; Rodents; Signal processing; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014568

Osteopontin (OPN) is a pleiotropic protein implicated in various inflammatory responses including ischemia-reperfusion (I-R) injury. Two distinct forms of the protein have been identified: an extensively studied secreted form (sOPN) and a less-well-known intracellular form (iOPN). Studies have shown that increased OPN expression parallels the time course of macrophage infiltration into injured tissue, a late event in the development of cerebral infarcts. sOPN has been suggested to promote remodeling of the extracellular matrix in the brain; the function of iOPN may be to facilitate certain signal transduction processes. Here, we studied OPN expression in adult male Sprague-Dawley rats subjected to global forebrain I-R injury. We found iOPN in the cytoplasm of both cortices and the hippocampus, but unexpectedly only the right cortex exhibited a marked increase in the iOPN level after 45 min of reperfusion. Acetaminophen, a drug recently shown to decrease apoptotic incidence, caspase-9 activation, and mitochondrial dysfunction during global I-R, significantly inhibited the increase in iOPN protein in the right cortex, suggesting a role for iOPN in the response to I-R injury in the right cortex.