title: TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS.
abstract: TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers [Csortos et al., 2008. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L440-L450]. Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability.
authors: Vascular Biology Center, Georgia Health Sciences University, Augusta, GA 30912, USA. cpoirier@georgiahealth.edu
authors: Christophe
authors: C
authors: Poirier
authors: Boris A
authors: BA
authors: Gorshkov
authors: Marina A
authors: MA
authors: Zemskova
authors: Natalia V
authors: NV
authors: Bogatcheva
authors: Alexander D
authors: AD
authors: Verin
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; C486763:Ppp1r16b protein, mouse; D012333:RNA, Messenger