Thiamine and oxidants interact to modify cellular calcium stores

Area of Science:

• Neuroscience
• Biochemistry
• Oxidative Stress Research

Background:

• Alzheimer's disease (AD) is associated with reduced thiamine (vitamin B1) activity and increased oxidative stress.
• Thiamine deficiency in animal models induces oxidative stress, suggesting a potential antioxidant role for thiamine.
• Oxidative stress impacts calcium-dependent cellular processes, which are known to be altered in AD.

Purpose of the Study:

• To directly assess whether thiamine possesses antioxidant properties.
• To investigate the physiological relevance of thiamine's antioxidant effects on calcium regulation in the context of AD.
• To determine if thiamine selectively targets reactive oxygen species (ROS) or reactive nitrogen species (RNS).

Main Methods:

• Cells were exposed to t-butyl-hydroperoxide (t-BHP) for ROS induction and 3-morpholinosydnonimine (SIN-1) for RNS induction.
• Dose-response curves were established to determine effective concentrations of t-BHP and SIN-1.
• Thiamine's effects on ROS/RNS production, endoplasmic reticulum (ER) calcium stores, and capacitative calcium entry (CCE) were measured.

Main Results:

• Thiamine reduced RNS production but did not significantly diminish ROS production in cells.
• Thiamine significantly decreased ER calcium stores but did not alter CCE.
• Thiamine mitigated the effects of RNS on CCE, but not the effects of ROS on ER calcium or CCE.

Conclusions:

• Thiamine demonstrates selective antioxidant activity, primarily by diminishing the impact of RNS rather than ROS.
• Thiamine influences calcium regulation, specifically affecting ER calcium stores and the response of CCE to RNS.
• Further research is needed to clarify the bidirectional relationship between thiamine availability and oxidative stress in AD.