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Thiamine and Oxidants Interact to Modify Cellular Calcium Stores

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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.

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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

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Acknowledgments

The work was supported by AG14930, AG14600, AG19589 and Burke Medical research Institute. The authors thank Dr. Arthur Cooper for his constructively critical comments. Abel Lajtha has been an inspiration to me for my whole career as a neurochemist. I had the honor of interacting with him in his roles in the American Society for Neurochemistry, Neurochemical Research and the Handbook for Neurochemistry. His activities have had a large impact on my career and the whole neurochemistry community. His vision for each of these has been fulfilled. He has always made time for me and has always encouraged me. His faith in me enabled me to accomplish goals that I would not have attempted. I am very grateful to Abel for being such a positive influence for so many years.

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Authors and Affiliations

  1. Burke Medical Research Institute, Weill Medical College of Cornell University, 785 Mamaroneck Ave, White Plains, NY, 10605, USA

    Hsueh-Meei Huang, Huan-Lian Chen & Gary E. Gibson

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  1. Hsueh-Meei Huang
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  2. Huan-Lian Chen
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  3. Gary E. Gibson
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Correspondence to Gary E. Gibson.

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Special issue article in honor of Dr. Abel Lajtha.

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Huang, HM., Chen, HL. & Gibson, G.E. Thiamine and Oxidants Interact to Modify Cellular Calcium Stores. Neurochem Res 35, 2107–2116 (2010). https://doi.org/10.1007/s11064-010-0242-z

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