DHCR24-knockout embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis because of dysfunction of caveolae and insulin-Akt-Bad signaling

Endocrinology
Xiuli LuHisao Seo

Abstract

The DHCR24 gene encodes an enzyme catalyzing the last step of cholesterol biosynthesis, the conversion of desmosterol to cholesterol. To elucidate the physiological significance of cholesterol biosynthesis in mammalian cells, we investigated proliferation of mouse embryonic fibroblasts (MEFs) prepared from DHCR24(-/-) mice. Both DHCR24(-/-) and wild-type MEFs proliferated in the presence of serum in culture media. However, the inhibition of external cholesterol supply by serum withdrawal induced apoptosis of DHCR24(-/-) MEFs, which was associated with a marked decrease in the intracellular and plasma membrane cholesterol levels, Akt inactivation, and Bad dephosphorylation. Insulin is an antiapoptotic factor capable of stimulating the Akt-Bad cascade, and its receptor (IR) is enriched in caveolae, cholesterol-rich microdomains of plasma membrane. We thus analyzed the association of IR and caveolae in the cholesterol-depleted MEFs. Subcellular fractionation and immunocytochemical analyses revealed that the IR and caveolin-1 contents were markedly reduced in the caveolae fraction of the MEFs, suggesting the disruption of caveolae, and that large amounts of IR were present apart from caveolin-1 on plasma membrane, indicating the un...Continue Reading

Citations

May 29, 2008·Cancer Metastasis Reviews·Jacky G GoetzIvan R Nabi
Apr 8, 2011·Cell Stress & Chaperones·Xiuli LuBing Gao
Jul 25, 2013·The International Journal of Biochemistry & Cell Biology·Wei LiuHuijun Duan
Sep 28, 2010·Journal of Bacteriology·Stacey D GilkRobert A Heinzen
Nov 7, 2007·Molecular and Cellular Biology·Katrin KuehnleM Hasan Mohajeri
Nov 26, 2008·Reproductive Biology and Endocrinology : RB&E·Russell L LeggMerrill J Christensen
Feb 5, 2011·Molecular Endocrinology·Olga Barca-MayoRoy E Weiss
Jan 30, 2013·PLoS Pathogens·Stacey D GilkRobert A Heinzen
Feb 4, 2010·Neuroscience·J Sánchez-WandelmerR Busto
Apr 9, 2009·Frontiers in Neuroendocrinology·Alessandro PeriMario Serio
Oct 4, 2008·Prostaglandins & Other Lipid Mediators·Koji FunahashiFukushi Kambe
May 22, 2009·Journal of Neurochemistry·Jana Sánchez-WandelmerRebeca Busto
Sep 11, 2012·Journal of Neurochemistry·Kymry T JonesMaarten E A Reith
May 12, 2009·The Biochemical Journal·Julian Stevenson, Andrew J Brown
Oct 8, 2013·Progress in Lipid Research·Eser J ZerenturkAndrew J Brown
Oct 28, 2009·Human & Experimental Toxicology·Yukiko KawashiroChisato Mori
Sep 19, 2014·Journal of Virology·George A WudiriAnthony V Nicola
Sep 20, 2020·The Journal of Membrane Biology·Parijat SarkarAmitabha Chattopadhyay
Mar 21, 2008·The Journal of Biological Chemistry·Maurice JansenElina Ikonen

❮ Previous
Next ❯

Related Concepts

Related Feeds

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

Caveolins & Signal Transduction

Caveolins are small proteins with a hairpin loop conformation that are located in the plasma membrane of various cell types where they bind cholesterol and interact with receptors essential for several signal transduction pathways. Here is the latest research.