Neurochemical Research

, Volume 35, Issue 12, pp 2107–2116

Thiamine and Oxidants Interact to Modify Cellular Calcium Stores

Authors

  • Hsueh-Meei Huang
    • Burke Medical Research InstituteWeill Medical College of Cornell University
  • Huan-Lian Chen
    • Burke Medical Research InstituteWeill Medical College of Cornell University
    • Burke Medical Research InstituteWeill Medical College of Cornell University
ORIGINAL PAPER

DOI: 10.1007/s11064-010-0242-z

Cite this article as:
Huang, H., Chen, H. & Gibson, G.E. Neurochem Res (2010) 35: 2107. doi:10.1007/s11064-010-0242-z

Abstract

Diminished thiamine (vitamin B1) dependent processes and oxidative stress accompany Alzheimer’s disease (AD). Thiamine deficiency in animals leads to oxidative stress. These observations suggest that thiamin may act as an antioxidant. The current experiments first tested directly whether thiamin could act as an antioxidant, and then examined the physiological relevance of the antioxidant properties on oxidant sensitive, calcium dependent processes that are altered in AD. The first group of experiments examined whether thiamin could diminish reactive oxygen species (ROS) or reactive nitrogen species (RNS) produced by two very divergent paradigms. Dose response curves determined the concentrations of t-butyl-hydroperoxide (t-BHP) (ROS production) or 3-morpholinosydnonimine ((SIN-1) (RNS production) to induce oxidative stress within cells. Concentrations of thiamine that reduced the RNS in cells did not diminish the ROS. The second group of experiments tested whether thiamine alters oxidant sensitive aspects of calcium regulation including endoplasmic reticulum (ER) calcium stores and capacitative calcium entry (CCE). Thiamin diminished ER calcium considerably, but did not alter CCE. Thiamine did not alter the actions of ROS on ER calcium or CCE. On the other hand, thiamine diminished the effect of RNS on CCE. These data are consistent with thiamine diminishing the actions of the RNS, but not ROS, on physiological targets. Thus, both experimental approaches suggest that thiamine selectively alters RNS. Additional experiments are required to determine whether diminished thiamine availability promotes oxidative stress in AD or whether the oxidative stress in AD brain diminishes thiamine availability to thiamine dependent processes.

Keywords

ThiamineOxidative stressNeurodegenerative diseaseCalcium

Abbreviations

BRCS

Bombesin-releasable calcium stores

BSS

Balanced salt solution

CCE

Capacitative calcium entry

CPA

Cyclopiazonic acid

[Ca2+]i

Cytosolic free calcium concentration

DCF

6-Carboxy-2′,7′-dichlorodihydro-fluorescein diacetate (acetoxymethyl ester)

DAF

Diacetate (4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate)

N2O3

Dinitrogen trioxide

DMEM

Dulbecco’s modified Eagle’s medium

ER

Endoplasmic reticulum

Fura-2

Fura-2-acetoxymethyl ester

GSNO

S-nitrosoglutathione

GSH

Glutathione

GSSG

Glutathione disulfide

Gpx

Glutathione peroxidase

GRx

Glutathione reductase

NO

Nitric oxide

OONO

Peroxinitrite

PBS

Phosphate-buffered saline

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

SIN-1

3-Morpholinosyndnonimine

t-BHP

Tert-butyl-hydroxyperoxide

t-bu-O·

Tert-butyloxyl

t-bu-OO·

t-butylperoxyl

TD

Thiamine deficiency

TSH

Thiamine thiol

Copyright information

© Springer Science+Business Media, LLC 2010