Cargando…

Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

Brain cells expend large amounts of energy sequestering calcium (Ca(2+)), while loss of Ca(2+) compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P), a parent substrate to several metabolic major pathways, including glycolysis. In seve...

Descripción completa

Detalles Bibliográficos
Autores principales: Cole, Jeffrey T., Kean, William S., Pollard, Harvey B., Verma, Ajay, Watson, William D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330244/
https://www.ncbi.nlm.nih.gov/pubmed/22529775
http://dx.doi.org/10.3389/fnmol.2012.00051
_version_ 1782229946746273792
author Cole, Jeffrey T.
Kean, William S.
Pollard, Harvey B.
Verma, Ajay
Watson, William D.
author_facet Cole, Jeffrey T.
Kean, William S.
Pollard, Harvey B.
Verma, Ajay
Watson, William D.
author_sort Cole, Jeffrey T.
collection PubMed
description Brain cells expend large amounts of energy sequestering calcium (Ca(2+)), while loss of Ca(2+) compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P), a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum (ER) to sequester Ca(2+). This led to the hypothesis that G6P regulates Ca(2+) accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA). Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, (45)Ca(2+) accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi) coupled with Ca(2+) accumulation was quantified. Addition of G6P significantly and decreased Ca(2+) accumulation in a dose-dependent fashion (1–10 mM). The reduction in Ca(2+) accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca(2+) accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca(2+) uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca(2+) dystasis caused by altered G6P regulation of SERCA activity.
format Online
Article
Text
id pubmed-3330244
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-33302442012-04-23 Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum Cole, Jeffrey T. Kean, William S. Pollard, Harvey B. Verma, Ajay Watson, William D. Front Mol Neurosci Neuroscience Brain cells expend large amounts of energy sequestering calcium (Ca(2+)), while loss of Ca(2+) compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P), a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum (ER) to sequester Ca(2+). This led to the hypothesis that G6P regulates Ca(2+) accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA). Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, (45)Ca(2+) accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi) coupled with Ca(2+) accumulation was quantified. Addition of G6P significantly and decreased Ca(2+) accumulation in a dose-dependent fashion (1–10 mM). The reduction in Ca(2+) accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca(2+) accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca(2+) uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca(2+) dystasis caused by altered G6P regulation of SERCA activity. Frontiers Media S.A. 2012-04-20 /pmc/articles/PMC3330244/ /pubmed/22529775 http://dx.doi.org/10.3389/fnmol.2012.00051 Text en Copyright © 2012 Cole, Kean, Pollard, Verma and Watson. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Neuroscience
Cole, Jeffrey T.
Kean, William S.
Pollard, Harvey B.
Verma, Ajay
Watson, William D.
Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum
title Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum
title_full Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum
title_fullStr Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum
title_full_unstemmed Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum
title_short Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum
title_sort glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330244/
https://www.ncbi.nlm.nih.gov/pubmed/22529775
http://dx.doi.org/10.3389/fnmol.2012.00051
work_keys_str_mv AT colejeffreyt glucose6phosphatereducescalciumaccumulationinratbrainendoplasmicreticulum
AT keanwilliams glucose6phosphatereducescalciumaccumulationinratbrainendoplasmicreticulum
AT pollardharveyb glucose6phosphatereducescalciumaccumulationinratbrainendoplasmicreticulum
AT vermaajay glucose6phosphatereducescalciumaccumulationinratbrainendoplasmicreticulum
AT watsonwilliamd glucose6phosphatereducescalciumaccumulationinratbrainendoplasmicreticulum