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Cofilin mediates ATP depletion-induced endothelial cell actin alterations

, : Cofilin mediates ATP depletion-induced endothelial cell actin alterations. American Journal of Physiology. Renal Physiology 290(6): F1398-F1407

Ischemia and sepsis lead to endothelial cell damage, resulting in compromised microvascular flow in many organs. Much remains to be determined regarding the intracellular structural events that lead to endothelial cell dysfunction. To investigate potential actin cytoskeletal-related mechanisms, ATP depletion was induced in mouse pancreatic microvascular endothelial cells (MS1). Fluorescent imaging and biochemical studies demonstrated a rapid and progressive increase in F-actin along with a decrease in G-actin at 60 min. Confocal microscopic analysis showed ATP depletion resulted in destruction of actin stress fibers and accumulation of F-actin aggregates. We hypothesized these actin alterations were secondary to dephosphorylation/activation of actin-depolymerizing factor (ADF)/cofilin proteins. Cofilin, the predominant isoform expressed in MS1 cells, was rapidly dephosphorylated/activated during ATP depletion. To directly investigate the role of cofilin activation on the actin cytoskeleton during ischemia, MS1 cells were infected with adenoviruses containing the cDNAs for wild-type Xenopus laevis ADF/cofilin green fluorescent protein [XAC(wt)-GFP], GFP, and the constitutively active and inactive isoforms XAC(S3A)-GFP and XAC(S3E)-GFP. The rate and extent of cortical actin destruction and actin aggregate formation were increased in ATP-depleted XAC(wt)-GFP- and XAC(S3A)-GFP- expressing cells, whereas increased actin stress fibers were observed in XAC(S3E)GFP- expressing cells. To investigate the upstream signaling pathway of ADF/cofilin, LIM kinase 1-GFP (LIMK1-GFP) was expressed in MS1 cells. Cells expressing LIMK1-GFP protein had higher levels of phosphorylated ADF/cofilin, increased stress fibers, and delayed F-actin cytoskeleton destruction during ATP depletion. These results strongly support the importance of cofilin regulation in ischemia-induced endothelial cell actin cytoskeleton alterations leading to cell damage and microvascular dysfunction.


PMID: 16434575

DOI: 10.1152/ajprenal.00194.2005

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Sinclair M.; Anthony V.C.; Iles T.D.; O'boyle R.N., 1985: Stock assessment problems in atlantic herring clupea harengus in the northwest atlantic. Total annual catches of Atlantic herring (C. harengus) in [North Atlantic Fisheries Organization] statistical areas 3-6 have declined steadily since 1968, and have not rebounded after management measures were implemented in the late 1970's (u...

Herrmann, H.-Werner; Edwards, T., 2006: Conraua goliath (goliath frog). Skittering locomotion. Herpetological Review 37(2): 202-203

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Crabtree, J.S.; Singleton, C.S.; Miele, L., 2016: Notch Signaling in Neuroendocrine Tumors. Carcinoids and neuroendocrine tumors (NETs) are a heterogeneous group of tumors that arise from the neuroendocrine cells of the GI tract, endocrine pancreas, and the respiratory system. NETs remain significantly understudied with respect to molecu...

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White, R.L., 1964: The Ama Looks At Environmental Health. Archives of Environmental Health 9: 589-591

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Friedlander, P., 1996: Rock and roll: a social history. This book chronicles the first 30 years of rock/pop music history. It reflects the musical and lyrical roots that are derived from the classic rock era (rock) and its status as a commodity produced under pressure to conform by the record industry...

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