A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells
Samo za registrovane korisnike
2009
Autori
Isenovic, Esma R.Fretaud, Maxence
Dobutović, Branislava
Sudar, Emina
Smiljanić, Katarina
Zarić, Božidarka L.
Trpkovic, Andreja
Marche, Pierre
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA(2)) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA(2) are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA(2) and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA(2) by 1.5-fold (p lt 0.01), which was blocked by the cPLA(2) inhibitor MAFP (10 mu M; 15 min). Similarly, the PI3K inhibitor LY294002 (10 mu M; 15 min) and ERK1/2 inhibitor PD98059 (20 mu M; 15 min) abolished the INS-mediated increase in cPLA(2) phosphorylation by 59% (p lt 0.001), and by 75% (p lt 0.001),... respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% (p lt 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% (p lt 0.001). The effect of INS on VSMCs proliferation was significantly (p lt 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA(2) and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA(2) activity. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
Ključne reči:
Vascular smooth muscle cells / INS / Proliferation / cPLA(2) / ERK1/2 / PI3KIzvor:
Cell Biology International, 2009, 33, 3, 386-392Izdavač:
- Academic Press Ltd- Elsevier Science Ltd, London
Finansiranje / projekti:
- Molekularni mehanizmi transdukcije hormonskih signala: Biološki markeri modifikacije i integracije signalnih puteva u fiziološkim i patofiziološkim stanjima (RS-MESTD-MPN2006-2010-143030)
- Republic of France, Ministry of Foreign Affairs
- Pavle Savic [337-00-359/2005-01/16]
- University Pierre and Marie Curie
- CNRS
DOI: 10.1016/j.cellbi.2009.01.010
ISSN: 1065-6995
PubMed: 19385036
WoS: 000263890200017
Scopus: 2-s2.0-61349124153
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Isenovic, Esma R. AU - Fretaud, Maxence AU - Dobutović, Branislava AU - Sudar, Emina AU - Smiljanić, Katarina AU - Zarić, Božidarka L. AU - Trpkovic, Andreja AU - Marche, Pierre PY - 2009 UR - https://cherry.chem.bg.ac.rs/handle/123456789/612 AB - Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA(2)) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA(2) are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA(2) and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA(2) by 1.5-fold (p lt 0.01), which was blocked by the cPLA(2) inhibitor MAFP (10 mu M; 15 min). Similarly, the PI3K inhibitor LY294002 (10 mu M; 15 min) and ERK1/2 inhibitor PD98059 (20 mu M; 15 min) abolished the INS-mediated increase in cPLA(2) phosphorylation by 59% (p lt 0.001), and by 75% (p lt 0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% (p lt 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% (p lt 0.001). The effect of INS on VSMCs proliferation was significantly (p lt 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA(2) and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA(2) activity. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. PB - Academic Press Ltd- Elsevier Science Ltd, London T2 - Cell Biology International T1 - A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells VL - 33 IS - 3 SP - 386 EP - 392 DO - 10.1016/j.cellbi.2009.01.010 ER -
@article{ author = "Isenovic, Esma R. and Fretaud, Maxence and Dobutović, Branislava and Sudar, Emina and Smiljanić, Katarina and Zarić, Božidarka L. and Trpkovic, Andreja and Marche, Pierre", year = "2009", abstract = "Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA(2)) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA(2) are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA(2) and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA(2) by 1.5-fold (p lt 0.01), which was blocked by the cPLA(2) inhibitor MAFP (10 mu M; 15 min). Similarly, the PI3K inhibitor LY294002 (10 mu M; 15 min) and ERK1/2 inhibitor PD98059 (20 mu M; 15 min) abolished the INS-mediated increase in cPLA(2) phosphorylation by 59% (p lt 0.001), and by 75% (p lt 0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% (p lt 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% (p lt 0.001). The effect of INS on VSMCs proliferation was significantly (p lt 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA(2) and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA(2) activity. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.", publisher = "Academic Press Ltd- Elsevier Science Ltd, London", journal = "Cell Biology International", title = "A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells", volume = "33", number = "3", pages = "386-392", doi = "10.1016/j.cellbi.2009.01.010" }
Isenovic, E. R., Fretaud, M., Dobutović, B., Sudar, E., Smiljanić, K., Zarić, B. L., Trpkovic, A.,& Marche, P.. (2009). A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells. in Cell Biology International Academic Press Ltd- Elsevier Science Ltd, London., 33(3), 386-392. https://doi.org/10.1016/j.cellbi.2009.01.010
Isenovic ER, Fretaud M, Dobutović B, Sudar E, Smiljanić K, Zarić BL, Trpkovic A, Marche P. A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells. in Cell Biology International. 2009;33(3):386-392. doi:10.1016/j.cellbi.2009.01.010 .
Isenovic, Esma R., Fretaud, Maxence, Dobutović, Branislava, Sudar, Emina, Smiljanić, Katarina, Zarić, Božidarka L., Trpkovic, Andreja, Marche, Pierre, "A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells" in Cell Biology International, 33, no. 3 (2009):386-392, https://doi.org/10.1016/j.cellbi.2009.01.010 . .