NO-Dependent Akt Inactivation by S-Nitrosylation as a Possible Mechanism of STZ-Induced Neuronal Insulin Resistance

Journal of Alzheimer's Disease : JAD
Fernanda CrunfliAndréa Silva Torrão

Abstract

Sporadic Alzheimer's disease (sAD) is associated with energy metabolism deficiency and impairment of insulin receptor (IR) signaling in the brain. In this context, low doses of intracerebroventricular (icv) injection of streptozotocin (STZ) in rodents has been used as an experimental model of sAD which leads to an insulin-resistant brain state and neurodegeneration. However, the STZ effects on brain insulin signaling-related proteins it is not appropriately elucidated. The aim of this study was to evaluate the beginning and progression of alterations in the brain IR pathway of rats after 1, 3, 5, and 7 days of STZ injection and investigate intracellular signaling involved on STZ induced insulin resistance. We observed that STZ injection causes cognitive impairment in the animals, a temporal variation of the insulin signaling-related proteins and apoptosis cell death in the hippocampus. We also have shown that STZ causes insulin resistance and impairment on phosphoinositide 3-kinase (PI3K) activity in the Neuro-2a cells through protein kinase B (Akt) inactivation by S-nitrosylation, which could upregulate GSK3-β activity. STZ ability to cause an insulin-resistant neuron state involves NO production and ROS production which may p...Continue Reading

References

Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·K S KosikD J Selkoe
Aug 1, 1993·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·K Plaschke, S Hoyer
Aug 28, 1998·Journal of Neural Transmission·L FrölichP Riederer
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·M P Scheid, J R Woodgett
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Mar 8, 2002·The Journal of Biological Chemistry·Wanli WeiJohn W Kusiak
Jun 27, 2002·Trends in Pharmacological Sciences·Laura GaspariniHuaxi Xu
May 23, 2003·Nature·Christopher J PhielPeter S Klein
Mar 5, 2004·Biochimica Et Biophysica Acta·Andrew M PetrosStephen W Fesik
Jul 2, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Boyer D WintersTimothy J Bussey
Sep 29, 2004·Cellular Signalling·Aleksandra Ellert-MiklaszewskaLiliana Konarska
Jan 6, 2005·The Journal of Biological Chemistry·Takashi YasukawaMasao Kaneki
Apr 22, 2006·Journal of Alzheimer's Disease : JAD·Nataniel Lester-CollSuzanne M de la Monte
Aug 19, 2006·Progress in Neurobiology·Lars P van der HeideMarten P Smidt
Sep 22, 2006·Journal of Alzheimer's Disease : JAD·Suzanne M de la MonteJack R Wands
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Dec 20, 2007·Journal of Neurochemistry·Claudie HooperSimon Lovestone
Jul 25, 2008·Luminescence : the Journal of Biological and Chemical Luminescence·Knox Van DykeDavid H Van Thiel
Aug 29, 2009·BMB Reports·Suzanne M de la Monte
Oct 15, 2009·Physiology & Behavior·Giordano Gubert ViolaDiogo Onofre Souza
Jan 26, 2011·Ageing Research Reviews·Sónia C CorreiaMark A Smith
Jun 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Naoki NumajiriTakashi Uehara
Mar 1, 2012·Biochimica Et Biophysica Acta·Amit GuptaChinmoy Sankar Dey
Aug 14, 2012·Journal of Alzheimer's Disease : JAD·Jogender MehlaYogendra Kumar Gupta
Aug 28, 2012·Physiology & Behavior·Taisa Oliveira SantosAndréa Silva Torrão
Jan 2, 2014·Biochemical Pharmacology·Suzanne M de la Monte, Ming Tong
Jan 10, 2014·Brain : a Journal of Neurology·Virginie StygelboutJean-Pierre Brion
Feb 18, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Fernanda G De FeliceSergio T Ferreira

❮ Previous
Next ❯

Citations

Oct 20, 2019·Bio-protocol·Daniel Moreira-SilvaDaniel C Carrettiero
Sep 29, 2020·Experimental Gerontology·Ruan Carlos Macêdo de MoraesAndrea da Silva Torrão
Jul 20, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rüdiger Hardeland

❮ Previous
Next ❯

Methods Mentioned

BETA
protein assay
PCR
ELISA

Software Mentioned

FlowJo
GraphPad Prism
Image Studio Digits

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

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.