Inhibition of phosphatidylinostol 3-kinase uncouples H2O2-induced senescent phenotype and cell cycle arrest in normal human diploid fibroblasts

Experimental Cell Research
Yong WangDaohong Zhou

Abstract

Exposure of WI38 human diploid fibroblasts (HDFs) to hydrogen peroxide (H2O2) induced premature senescence. The senescent HDFs were permanently arrested and exhibited a senescent phenotype including enlarged and flattened cell morphology and increased senescence-associated beta-galactosidase (SA-beta-gal) activity. The induction of HDF senescence was associated with an activation of p53, increased expression of p21Cip1/WAF1, and hypophosphorylation of retinoblastoma protein (Rb), while no changes in the expression of p16Ink4a, p27Kip1, and p14Arf were observed. Exposure of WI38 cells to H2O2 also selectively activated phosphatidylinostol 3-kinase (PI3 kinase) and mitogen-activated protein kinase (MAPK) kinase (MEK), while no changes in p38 MAPK and Jun kinase (JNK) activities were observed. Selective inhibition of PI3 kinase activity with LY294002 abrogated H2O2-induced cell enlargement and flattened morphology and significantly attenuated the increase in SA-beta-gal activity, but did not affect H2O2-induced cell cycle arrest. In contrast, selective inhibition of MEK and p38 MAPK with PD98059 and SB203580, respectively, produced no significant effect on H2O2-induced senescent phenotype and cell cycle arrest. These findings demo...Continue Reading

References

Oct 28, 1994·Biochemical and Biophysical Research Communications·V Sanchez-MargáletC K Sung
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·Q Chen, B N Ames
Jun 2, 1997·The Journal of Cell Biology·A PtasznikA Hayek
Dec 10, 1999·Experimental Cell Research·W Wei, J M Sedivy
May 8, 2001·Molecular and Cellular Biology·K Alexander, P W Hinds
Jun 8, 2001·Annual Review of Biochemistry·B VanhaesebroeckM D Waterfield
Nov 8, 2001·Current Opinion in Cell Biology·M Serrano, M A Blasco
Jan 30, 2002·Cellular and Molecular Life Sciences : CMLS·K MatuokaT Takenawa
Feb 28, 2002·The Journal of Pharmacology and Experimental Therapeutics·Victoria C TuQin M Chen
Jun 27, 2002·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Richard Marcotte, Eugenia Wang
Dec 10, 2002·Experimental Gerontology·Antonello LorenziniVincent J Cristofalo
Jul 10, 2003·Archives of Gerontology and Geriatrics·Koozi MatuokaTadaomi Takenawa
Dec 6, 2006·The Journal of Biological Chemistry·Maria TresiniVincent J Cristofalo
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos
Sep 21, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Julieann RaderJohn M Maris

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Citations

Oct 22, 2013·International Journal of Oncology·Hongmei LuoGavin Y Wang
May 8, 2009·Cellular and Molecular Life Sciences : CMLS·Eun Seong HwangHyun Tae Kang
Mar 2, 2010·Biological & Pharmaceutical Bulletin·Mi Jin ChoiEun Ju Cho
Apr 7, 2011·Biological & Pharmaceutical Bulletin·Kyohei OyamaKoichi Sakurai
Apr 19, 2013·Biogerontology·F BonominiR Rezzani
Jun 23, 2011·Age·Liliana MatosHenrique Almeida
May 21, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Hongmei LuoGavin Y Wang
Jul 12, 2008·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Susumu Ohshima
Jul 24, 2010·Annals of the New York Academy of Sciences·You-Mie KimGyesoon Yoon
Dec 9, 2014·Cell Cycle·Mikhail V Blagosklonny
Nov 26, 2010·International Journal of Radiation Oncology, Biology, Physics·Yong WangDaohong Zhou
Jul 12, 2008·Respiratory Medicine·Stefan KarraschRudolf A Jörres
Apr 11, 2012·International Journal of Molecular Sciences·Liujing GuoZebin Mao
Oct 27, 2006·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Werner J H KoopmanPeter H G M Willems
Mar 9, 2006·Journal of Cellular Physiology·Claudio TorresVincent J Cristofalo
May 8, 2020·Aging·Hyun-Ji ChoYoung-Sam Lee
Apr 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patrick LaplanteMarie-Josée Hébert
Jan 15, 2015·Oncotarget·Olga V Leontieva, Mikhail V Blagosklonny
Jul 21, 2021·Biochemical and Biophysical Research Communications·Roman E UshakovElena B Burova
Mar 17, 2009·Burns : Journal of the International Society for Burn Injuries·Michael MullerPeter K M Maitz

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