title: Differences in phosphodiesterase 3A and 3B expression after ischemic insult.
abstract: Phosphodiesterase (PDE) exists in the cardiovascular system, adipose tissue and platelets, and its inhibition increases the cellular levels of cAMP, which could activate cAMP-responsive element binding protein (pCREB). The present study was designed to map the expression of PDE3A/B in the forebrain and define the time course of PDE3 expression in the ischemic boundary zone after ischemia. The number of PDE3A-positive cells (neurons and endothelial cells) remained unchanged, while PDE3B-positive cells gradually increased after ischemia/reperfusion. In the corpus callosum, PDE3B was expressed in oligodendrocytes, oligodendrocyte progenitor cells, and astrocytes. PDE3B-expressing astrocytes showed gradual increase after ischemia/reperfusion. In the cortex, the majority of PDE3B-expressing cells before ischemia were neurons, though few were astrocytes. Ischemic insult resulted in gradual increase in PDE3B-expressing astrocytes and neurons, with larger increase in astrocytes. Expression of brain derived neurotrophic factor (BDNF) and B-cell leukemia/lymphoma 2 protein (Bcl-2) was detected in pCREB-positive cells, not in PDE3B-positive cells. Our results demonstrated that ischemic insult increased PDE3B expression, but not PDE3A, and changed the number and type of cells in a time-dependent manner. The variation of PDE3B-expression in the brain might play a crucial pathophysiological role, and regulation of PDE3B production might protect against ischemic brain damage.
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Mitome-Mishima
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Miyamoto
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Oishi
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Takao
authors.initials: T
authors.lastname: Urabe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003337:Corpus Callosum / Q000201:enzymology / Q000473:pathology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D015424:Reperfusion
chemical_list: C491049:Aif1 protein, mouse; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D050882:CREB-Binding Protein; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D010751:Phosphopyruvate Hydratase