Lysophosphatidic acid and adenylyl cyclase inhibitor increase proliferation of senescent human diploid fibroblasts by inhibiting adenosine monophosphate-activated protein kinase

Rejuvenation Research
Ji-Heon RhimSang-Chul Park

Abstract

This study was designed to elucidate the molecular mechanism underlying lysophosphatidic acid (LPA) and adenylyl cyclase inhibitor SQ22536 (ACI)-induced senescent human diploid fibroblast (HDF) proliferation. Because adenosine monophosphate (AMP)-activated protein kinase (AMPK) is known to inhibit cell proliferation, we examined the phosphorylation status of AMPK and p53 and the expression level of p21(waf1/cip1) after treating HDFs with LPA and ACI. Phosphorylation of AMPKalpha on threonine-172 (p-Thr172-AMPKalpha) increases its catalytic activity but phosphorylation on serine-485/491 (p-Ser485/491-AMPKalpha) reduces the accessibility of the Thr172 phosphorylation site thereby inhibiting its catalytic activity. LPA increased p-Ser485/491-AMPKalpha, presumably by activating cAMP-dependent protein kinase (PKA). However, ACI reduced p-Thr172-AMPKalpha by inhibiting the LKB signaling. Our data demonstrated that both LPA and ACI inhibit the catalytic activity of AMPKalpha and p53 by differentially regulating phosphorylation of AMPKalpha, causing increased senescent cell proliferation. These findings suggest that the proliferation potential of senescent HDFs can be modulated through the regulation of the AMPK signaling pathway.

References

Apr 1, 1995·Experimental Cell Research·P AtadjaK Riabowol
Jul 9, 1993·Science·R TaussigA G Gilman
Apr 1, 1997·Current Opinion in Cell Biology·W H MoolenaarG C Zondag
Sep 26, 1997·The Journal of Biological Chemistry·K I MitchelhillB E Kemp
Jan 22, 2000·The Biochemical Journal·S C SteinD Carling
May 20, 2000·Annals of the New York Academy of Sciences·W H Moolenaar
Apr 28, 2001·Prostaglandins & Other Lipid Mediators·N Fukushima, J Chun
Mar 21, 2003·Biochemical and Biophysical Research Communications·Ik-Soon JangSang-Chul Park
Aug 2, 2003·The Journal of Biological Chemistry·Suzanne KovacicJason R B Dyck
Nov 15, 2003·Current Biology : CB·Angela WoodsDavid Carling
Jan 20, 2004·Nature Structural & Molecular Biology·Christine C MilburnDaan M F van Aalten
Feb 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Reuben J ShawLewis C Cantley
Feb 1, 2005·Trends in Pharmacological Sciences·Zhijun LuoNeil B Ruderman
May 4, 2005·Molecular Cell·Russell G JonesCraig B Thompson
Jun 28, 2005·The Journal of Biological Chemistry·Rebecca L HurleyLee A Witters
Jul 20, 2005·The Journal of Biological Chemistry·Annett Hahn-WindgassenNissim Hay
Jan 24, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Carrie-Lynn M SoltysJason R B Dyck
Apr 15, 2006·The Journal of Physiology·Hiroyuki MotoshimaEiichi Araki
Jul 11, 2006·The Journal of Clinical Investigation·Yun Chau Long, Juleen R Zierath

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Citations

May 12, 2010·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Ji Heon RhimSang Chul Park
Jan 23, 2016·The Journal of Biological Chemistry·Kimberly A CoughlanAsish K Saha

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