Abstract:
:Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ectopic F(1)-ATPase stimulates the production of extracellular ADP that activates a P2Y(13)-mediated high-density lipoprotein (HDL) endocytosis pathway. However, P2Y(13)-dependent signalling pathway has never been described yet. The current study demonstrates a major role of cytoskeleton reorganization in F(1)-ATPase/P2Y(13)-dependent HDL endocytosis under the control of the small GTPase RhoA and its effector ROCK I. Indeed human hepatocytes (HepG(2) cells) stimulated by ADP or AR-C69931MX (both P2Y(13) agonists) showed a high specific activation of RhoA; in addition, inhibition of Rho proteins by C3 exoenzyme impairs HDL endocytosis whereas a constitutively active form of RhoA stimulates HDL endocytosis at the same level as under F(1)-ATPase/P2Y(13) activation. Pharmacological inhibition of ROCK activity decreased HDL endocytosis following stimulation by apoA-I (F(1)-ATPase ligand), ADP or AR-C69931MX and specific siRNA ROCK I extinction prevented the stimulation of HDL endocytosis without effect of ROCK II extinction. The functional involvement of ROCK I downstream F(1)-ATPase/P2Y(13) was confirmed by the strong enrichment of the membrane fraction in ROCK I and by the requirement of actin polymerization in hepatocyte HDL endocytosis. These results allow the identification of the molecular events downstream P2Y(13) receptor activation for a better understanding of hepatocyte HDL endocytosis, the latest step in reverse cholesterol transport.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Malaval C,Laffargue M,Barbaras R,Rolland C,Peres C,Champagne E,Perret B,Tercé F,Collet X,Martinez LOdoi
10.1016/j.cellsig.2008.09.016subject
Has Abstractpub_date
2009-01-01 00:00:00pages
120-7issue
1eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00291-Xjournal_volume
21pub_type
杂志文章abstract::We have compared a new commercially available non-radioactive protein kinase C (PKC) activity assay based on the fluorescent [A9,10K11]glycogen synthase1-11 analogue C1-peptide with a classical radioactive assay based on myelin basic protein4-14 (MBP4-14) and other substrates. The C1-peptide had lower affinity for PKC...
journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2020.109886
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.10.017
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abstract::Skeletal muscle plays a major role in regulating whole body glucose metabolism. Akt and Rac1 are important regulators of insulin-stimulated glucose uptake in skeletal muscle. However the relative role of each pathway and how they interact are not understood. Here we delineate how Akt and Rac1 pathways signal to increa...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.11.007
更新日期:2014-02-01 00:00:00
abstract::As a member of the Rab small GTPase family, Rab11a has been shown to be involved in different vesicle trafficking processes. In earlier work we identified Rab11a to be present in GLUT4-containing vesicles after insulin stimulation and showed its involvement in insulin-dependent glucose uptake. However, it remained elu...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.10.008
更新日期:2007-04-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.05.008
更新日期:2013-09-01 00:00:00
abstract::Nephrin, an important structural and signal molecule of podocyte slit-diaphragm (SD), has been suggested to contribute to the angiotensin II (Ang II)-induced podocyte injury. Caveolin-1 has been demonstrated to play a crucial role in signaling transduction. In the present study, we evaluated the role of caveolin-1 in ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.09.022
更新日期:2012-02-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2004.09.013
更新日期:2005-03-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.01.013
更新日期:2011-05-01 00:00:00
abstract::We have previously shown that N18TG2 neuroblastoma cells express the type 6 adenylyl cyclase and that preincubation with nitric oxide (NO) attenuates Gs- and forskolin-stimulated activity. Here we show that this inhibition reflects a direct action of NO on the adenylyl cyclase. Preincubation of N18TG2 cell membranes a...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(99)00082-0
更新日期:2000-04-01 00:00:00
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doi:10.1016/0898-6568(92)90073-h
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journal_title:Cellular signalling
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更新日期:2009-11-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.05.017
更新日期:2008-10-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.10.007
更新日期:2017-01-01 00:00:00
abstract::Adenosine and its analogues inhibited increases in divalent cation influx stimulated by platelet-activating factor (PAF) and formyl-methionyl-leucyl-phenylalanine (FMLP) in a dose-dependent fashion. This effect was antagonized by theophylline, an adenosine receptor antagonist. When extracellular adenosine was removed ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(92)90023-2
更新日期:1992-09-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2010.01.013
更新日期:2010-07-01 00:00:00
abstract::Activation of β2-adrenergic receptor (β2AR) and deorphanized GPR55 has been shown to modulate cancer growth in diverse tumor types in vitro and in xenograft models in vivo. (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a bivalent compound that agonizes β2AR but inhibits GPR55-mediated pro-oncogenic responses. ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.05.006
更新日期:2017-08-01 00:00:00
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2018.12.005
更新日期:2019-02-01 00:00:00
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2020.109729
更新日期:2020-10-01 00:00:00
abstract::Macrophages are projected as one of the key players responsible for the progression of cancer. Classically activated (M1) macrophages are pro-inflammatory and have a central role in host defense, while alternatively activated (M2) macrophages are associated with immunosuppression. Macrophages residing at the site of n...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.03.013
更新日期:2015-07-01 00:00:00
abstract::Angiotensin II (AII) in 1-10 nM concentrations has an in vivo immunostimulating effect on human neutrophils. The release of superoxide anions and leukotrienes (LTs) is significantly increased by 10 nM AII-stimulated neutrophils of patients with hypercholesterolaemia (HCH). These oxidizing agents may be involved in the...
journal_title:Cellular signalling
pub_type: 杂志文章
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更新日期:2002-09-01 00:00:00