scholarly journals cAMP-stimulated Na+ transport in H441 distal lung epithelial cells: role of PKA, phosphatidylinositol 3-kinase, and sgk1

2004 ◽  
Vol 287 (4) ◽  
pp. L843-L851 ◽  
Author(s):  
Christie P. Thomas ◽  
Jason R. Campbell ◽  
Patrick J. Wright ◽  
Russell F. Husted
Keyword(s):  
Apical Cell ◽  
P38 Map Kinase ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
Phosphatidylinositol 3 Kinase ◽  
Transport Pathway ◽  
Early Effect ◽  
Sustained Effect ◽  
Phosphatidylinositol 3

H441 cells, a bronchiolar epithelial cell line, develop a cAMP-regulated benzamil-sensitive Na+ transport pathway on permeable supports (Itani OA, Auerbach SD, Husted RF, Volk KA, Ageloff S, Knepper MA, Stokes JB, Thomas CP. Am J Physiol Lung Cell Mol Physiol 282: L631–L641, 2002). To understand the molecular basis for the stimulation of Na+ transport, we delineated the role of specific intracellular pathways and examined the effect of cAMP on αβγ-epithelial Na+ channel (ENaC) and sgk1 expression. Na+ transport increases within 5 min of cAMP stimulation and is sustained for >24 h. The sustained effect of cAMP on Na+ transport is abolished by LY-294002, an inhibitor of phosphatidylinositol 3-kinase, by H89, an inhibitor of PKA, or by SB-202190, an inhibitor of p38 MAP kinase. The sustained effect of cAMP was associated with increases in α-ENaC mRNA and protein but without a detectable increase in βγ-ENaC and sgk1. The early effect of cAMP on Na+ transport is brefeldin sensitive and is mediated via PKA. These results are consistent with a model where the early effect of cAMP is to increase trafficking of Na+ channels to the apical cell surface whereas the sustained effect requires the synthesis of α-ENaC.

Pneumococci induced TLR- and Rac1-dependent NF-κB-recruitment to the IL-8 promoter in lung epithelial cells

2006 ◽  
Vol 290 (4) ◽  
pp. L730-L737 ◽  
Author(s):  
Bernd Schmeck ◽  
Sylvia Huber ◽  
Kerstin Moog ◽  
Janine Zahlten ◽  
Andreas C. Hocke ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Activation ◽  
Rho Gtpase ◽  
Dominant Negative ◽  
Lung Epithelial Cells ◽  
Dominant Negative Mutant ◽  
Epithelial Cell Line ◽  
Phosphatidylinositol 3 Kinase ◽  
Lung Epithelial ◽  
Phosphatidylinositol 3

Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia. The respiratory epithelium constitutes the first line of defense against invading lung pathogens, including pneumococci. We analyzed the involvement of Toll-like receptors (TLR) and Rho-GTPase signaling in the activation of human lung epithelial cells by pneumococci. S. pneumoniae induced release of interleukin-8 (IL-8) by human bronchial epithelial cell line BEAS-2B. Specific inhibition of Rac1 by Nsc23766 or a dominant-negative mutant of Rac1 strongly reduced cytokine release. In addition, pneumococci-related cell activation (IL-8 release, NF-κB-activation) depended on MyD88, phosphatidylinositol 3-kinase, and Cdc42 but not on RhoA. Pneumococci enhanced TLR1 and TLR2 mRNA expression in BEAS-2B cells, whereas TLR4 and TLR6 expression was constitutively high. TLR1 and 2 synergistically recognized pneumococci in cotransfection experiments. TLR4, TLR6, LPS-binding protein, and CD14 seem not to be involved in pneumococci-dependent cell activation. At the IL-8 gene promoter, recruitment of phosphorylated NF-κB subunit p65 was blocked by inhibition of Rac1, whereas binding of the phosphorylated activator protein-1 subunit c-Jun to the promoter was not diminished. In summary, these results suggest that S. pneumoniae activate human epithelial cells by TLR1/2 and a phosphatidylinositol 3-kinase- and Rac1-dependent NF-κB-recruitment to the IL-8 promoter.

scholarly journals Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions. Vol. 278 (2003) 49239-49245

2004 ◽  
Vol 279 (7) ◽  
pp. 6204
Author(s):  
Parimal Sheth ◽  
Shyamali Basuroy ◽  
Chunying Li ◽  
Anjaparavanda P. Naren ◽  
Radhakrishna K. Rao
Keyword(s):  
Oxidative Stress ◽  
Tight Junctions ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

scholarly journals Novel Role of Phosphatidylinositol 3-Kinase in CD28-mediated Costimulation

2000 ◽  
Vol 276 (12) ◽  
pp. 9003-9008 ◽  
Author(s):  
Yohsuke Harada ◽  
Eri Tanabe ◽  
Ryosuke Watanabe ◽  
Bonnie D. Weiss ◽  
Akira Matsumoto ◽  
...  
Keyword(s):  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

scholarly journals PI(4,5)P2 controls slit diaphragm formation and endocytosis in Drosophila nephrocytes

2021 ◽  
Author(s):  
Max Gass ◽  
Sarah Borkowsky ◽  
Marie-Luise Lotz ◽  
Rita Schroeter ◽  
Pavel Nedvetsky ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Model System ◽  
Dominant Negative ◽  
Slit Diaphragm ◽  
Phosphatidylinositol 3 Kinase ◽  
Ectopic Activation ◽  
Phosphatidylinositol 4 ◽  
Asymmetrically Distributed ◽  
Phosphatidylinositol 3

Drosophila nephrocytes are an emerging model system for mammalian podocytes and podocyte-associated diseases. Like podocytes, nephrocytes exhibit characteristics of epithelial cells, but the role of phospholipids in polarization of these cells is yet unclear. In epithelia phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) and phosphatidylinositol(3,4,5)-trisphosphate (PI(3,4,5)P3) are asymmetrically distributed in the plasma membrane and determine apical-basal polarity. Here we demonstrate that both phospholipids are present in the plasma membrane of nephrocytes, but only PI(4,5)P2 accumulates at slit diaphragms. Knockdown of Skittles, a phosphatidylinositol(4)phosphate 5-kinase, which produces PI(4,5)P2, abolished slit diaphragm formation and led to strongly reduced endocytosis. Notably, reduction in PI(3,4,5)P3 by overexpression of PTEN or expression of a dominant-negative phosphatidylinositol-3-Kinase did not affect nephrocyte function, whereas enhanced formation of PI(3,4,5)P3 by constitutively active phosphatidylinositol-3-Kinase resulted in strong slit diaphragm and endocytosis defects by ectopic activation of the Akt/mTOR pathway. Thus, PI(4,5)P2 but not PI(3,4,5)P3 is essential for slit diaphragm formation and nephrocyte function. However, PI(3,4,5)P3 has to be tightly controlled to ensure nephrocyte development.

Phosphatidylinositol 3-Kinase and Prostaglandylinositol Cyclic Phosphate (Cyclic PIP), a Mediator of Insulin Action, in the Signal Transduction of Insulin

2000 ◽  
Vol 381 (11) ◽  
pp. 1139-1141 ◽  
Author(s):  
A. Gypakis ◽  
H.K. Wasner
Keyword(s):  
Insulin Receptor ◽  
Glucose Transport ◽  
Functional Role ◽  
Specific Inhibitor ◽  
Insulin Receptor Substrate ◽  
Phosphatidylinositol 3 Kinase ◽  
Downstream Signaling ◽  
Cyclic Phosphate ◽  
Phosphatidylinositol 3

Abstract It has been suggested that downstream signaling from the insulin receptor to the level of the protein kinases and protein phosphatases is accomplished by prostaglandylinositol cyclic phosphate (cyclic PIP), a proposed second messenger of insulin. However, evidence points also to both phosphatidylinositol 3-kinase, which binds to the tyrosine phosphorylated insulin receptor substrate-1, and the Ras complex in insulin's downstream signaling. We have examined whether a correlation exists between these various observations. It was found that wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase, prevented insulin-induced, as well as cyclic PIP-induced activation of glucose transport, indicating that PI 3-kinase action on glucose transport involves downstream signaling of both insulin and cyclic PIP. Wortmannin has no effect on cyclic PIP synthase activity nor on the substrate production for cyclic PIP synthesis either, indicating that the functional role of PI 3-kinase is exclusively downstream of cyclic PIP.

Role of Phosphatidylinositol-3 Kinase Pathway in NMDA Preconditioning: Different Mechanisms for Seizures and Hippocampal Neuronal Degeneration Induced by Quinolinic Acid

2018 ◽  
Vol 34 (3) ◽  
pp. 452-462 ◽  
Author(s):  
Leandra C. Constantino ◽  
Luisa B. Binder ◽  
Samuel Vandresen-Filho ◽  
Giordano G. Viola ◽  
Fabiana K. Ludka ◽  
...  
Keyword(s):  
Quinolinic Acid ◽  
Neuronal Degeneration ◽  
Phosphatidylinositol 3 Kinase ◽  
Nmda Preconditioning ◽  
Kinase Pathway ◽  
Phosphatidylinositol 3

Hepatic glutamine transporter activation in burn injury: role of amino acids and phosphatidylinositol-3-kinase

2000 ◽  
Vol 278 (4) ◽  
pp. G532-G541 ◽  
Author(s):  
Timothy M. Pawlik ◽  
Rüdiger Lohmann ◽  
Wiley W. Souba ◽  
Barrie P. Bode
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Burn Injury ◽  
Cell Swelling ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitors ◽  
Glutamine Transporter ◽  
Hypermetabolic State ◽  
Phosphatidylinositol 3

Burn injury elicits a marked, sustained hypermetabolic state in patients characterized by accelerated hepatic amino acid metabolism and negative nitrogen balance. The transport of glutamine, a key substrate in gluconeogenesis and ureagenesis, was examined in hepatocytes isolated from the livers of rats after a 20% total burn surface area full-thickness scald injury. A latent and profound two- to threefold increase in glutamine transporter system N activity was first observed after 48 h in hepatocytes from injured rats compared with controls, persisted for 9 days, and waned toward control values after 18 days, corresponding with convalescence. Further studies showed that the profound increase was fully attributable to rapid posttranslational transporter activation by amino acid-induced cell swelling and that this form of regulation may be elicited in part by glucagon. The phosphatidylinositol-3-kinase (PI3K) inhibitors wortmannin and LY-294002 each significantly attenuated transporter stimulation by amino acids. The data suggest that PI3K-dependent system N activation by amino acids may play an important role in fueling accelerated hepatic nitrogen metabolism after burn injury.

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