Identification of novel cell survival regulation in diabetic embryopathy via phospholipidomic profiling

Biochemical and Biophysical Research Communications
Lixue CaoZhiyong Zhao

Abstract

Diabetes mellitus in early pregnancy causes birth defects by disturbing metabolic homeostasis and increasing programmed cell death in the embryo. Over-activation of phospholipase Cβ3 and γ1 suggests disturbed phospholipid metabolism, which is an important in regulation of cell signaling and activity. Metabolomic examinations reveal significant changes in the profile of phospholipid metabolism. Among the metabolites, levels of phosphatidylinositol bisphosphate (PIP2) are increased. PIP2 effector PTEN (phosphatase and tensin homolog deleted on chromosome 10) is activated. Activation of protein kinase Bα (PKBα, or AKT1) and mTOR (mechanistic target of rapamycin) is decreased. Inhibition of PLCs and PTEN suppresses over-generation of reactive oxygen species and inhibition of PLCs prevents fragmentation of mitochondria in neural stem cells cultured in high glucose. These observations suggest that maternal hyperglycemia disrupts phospholipid metabolism, leading to perturbation of mitochondrial dynamics and redox homeostasis and suppression of the PKB-mTOR cell survival signaling in the embryos.

References

Apr 29, 1998·Annual Review of Physiology·R N Kolesnick, M Krönke
Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·K E HentgesA S Peterson
Jun 1, 2002·Science·Lewis C Cantley
Jun 5, 2003·The Journal of Biological Chemistry·Zhong-Zhou YangBrian A Hemmings
Sep 19, 2003·Nature Reviews. Genetics·Andrew J CoppJennifer N Murdoch
Oct 17, 2003·The Journal of Physiology·Julio F Turrens
May 18, 2005·Progress in Lipid Research·Lucia ManzoliLucio Cocco
Feb 7, 2006·American Journal of Obstetrics and Gynecology·E Albert ReeceDanny Dhanasekaran
Jul 20, 2006·Annual Review of Nutrition·Steven H Zeisel
Sep 16, 2006·FEBS Letters·Michael Schlame, Mindong Ren
Oct 13, 2006·Annual Review of Pharmacology and Toxicology·Sten OrreniusBoris Zhivotovsky
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Jun 24, 2008·Nature Reviews. Neuroscience·Andrew B KnottElla Bossy-Wetzel
Aug 5, 2008·American Journal of Obstetrics and Gynecology·Adolfo CorreaE Albert Reece
Jan 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alonzo H Ross, Arne Gericke
Jan 18, 2012·The Biochemical Journal·Thomas D MullenLina M Obeid
Mar 29, 2012·Advances in Experimental Medicine and Biology·Lily ZengPhilip M Newton
Apr 3, 2012·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Yuanning CaoE Albert Reece
Apr 5, 2012·Nature Reviews. Molecular Cell Biology·Min Sup SongPier Paolo Pandolfi
Sep 1, 2012·Science·Richard J Youle, Alexander M van der Bliek
Sep 7, 2012·Cold Spring Harbor Perspectives in Biology·Brian A Hemmings, David F Restuccia
Sep 27, 2012·Biochimica Et Biophysica Acta·Paolo Fagone, Suzanne Jackowski
Nov 13, 2012·Annual Review of Physiology·Ganesh Kadamur, Elliott M Ross
May 25, 2013·Clinics in Laboratory Medicine·Zhiyong Zhao, E Albert Reece
Jun 19, 2013·Advances in Experimental Medicine and Biology·Mahua Chakraborty, Xian-Cheng Jiang
Jun 19, 2013·Advances in Experimental Medicine and Biology·Robert D RiehleAlexei Degterev
Jul 25, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kay O SchinkHarald Stenmark
Apr 30, 2014·Communicative & Integrative Biology·Pablo Garcia-Junco-Clemente, Peyman Golshani
Jun 7, 2014·Annual Review of Biochemistry·Carolyn A Worby, Jack E Dixon
Jul 18, 2014·Annual Review of Neuroscience·Nicholas D E Greene, Andrew J Copp
Dec 2, 2014·American Journal of Obstetrics and Gynecology·Peixin YangRinat Gabbay-Benziv
Dec 3, 2014·Advances in Biological Regulation·Laura SpinelliNicholas R Leslie

❮ Previous
Next ❯

Citations

Sep 13, 2017·Scientific Reports·Gyuyoup KimZhiyong Zhao
Apr 12, 2017·Proceedings of the National Academy of Sciences of the United States of America·Zhiyong ZhaoE Albert Reece

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis