Phosphodiesterase isoform-specific expression induced by traumatic brain injury.
Traumatic brain injury (TBI) results in significant inflammation which contributes to the evolving pathology. Previously, we have demonstrated that cyclic AMP (cAMP), a molecule involved in inflammation, is down-regulated after TBI. To determine the mechanism by which cAMP is down-regulated after TBI, we determined whether TBI induces changes in phosphodiesterase (PDE) expression. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury (FPI) or sham injury, and the ipsilateral, parietal cortex was analyzed by western blotting. In the ipsilateral parietal cortex, expression of PDE1A, PDE4B2, and PDE4D2, significantly increased from 30 min to 24 h post-injury. PDE10A significantly increased at 6 and 24 h after TBI. Phosphorylation of PDE4A significantly increased from 6 h to 7 days post-injury. In contrast, PDE1B, PD4A5, and PDE4A8 significantly decreased after TBI. No changes were observed with PDE1C, PDE3A, PDE4B1/3, PDE4B4, PDE4D3, PDE4D4, PDE8A, or PDE8B. Co-localization studies showed that PDE1A, PDE4B2, and phospho-PDE4A were neuronally expressed, whereas PDE4D2 was expressed in neither neurons nor glia. These findings suggest that therapies to reduce inflammation after TBI could be facilitated with targeted therapies, in particular for PDE1A, PDE4B2, PDE4D2, or PDE10A.
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Anthony A
AA
Oliva
Yuan
Y
Kang
Concepcion
C
Furones
Ofelia F
OF
Alonso
Olga
O
Bruno
W Dalton
WD
Dietrich
Coleen M
CM
Atkins
D000818:Animals; D001930:Brain Injuries / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D000242:Cyclic AMP; C512064:PDE10A protein, rat; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C546993:PDE4B protein, rat; C528468:PDE4D protein, rat; C517263:Pde1a protein, rat; C517269:Pde1b protein, rat