کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5926451 | 1571341 | 2011 | 4 صفحه PDF | دانلود رایگان |
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.
⺠Timap deficiency exacerbates LPS-induced pulmonary vascular leak. ⺠TIMAP mRNA level is down-regulated by LPS in different species. ⺠Timap promoter activity is not down-regulated by LPS. ⺠TIMAP mRNA level is up-regulated by PKA.
Journal: Respiratory Physiology & Neurobiology - Volume 179, Issues 2â3, 15 December 2011, Pages 334-337