Abstract
Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.
Highlights
Calcium-release activated channels (CRACs) are store-operated calcium channels located at the plasma membrane that are activated by low intracellular calcium store concentrations, resulting in a sustained increase of the cytosolic calcium concentration
Resveratrol has not been shown to exert a direct effect on CRAC channels [69] (Table 1) it has been suggested that resveratrol acts indirectly on store-operated calcium entry (SOCE)
Resveratrol is a potent modulator of many cellular calcium signaling pathways (Table 1)
Summary
Resveratrol is a stilbenoid commonly found in the roots of Japanese Knotweed and the skin of red grapes. Some of the proposed mechanisms include antioxidant, anticarcinogenic, anti-inflammatory, anti-aging [8], and anti-nociceptive functions indicating the potential of resveratrol as therapeutic agent for preventing and ameliorating a wide range of pathologies [9,10,11,12,13,14], including neurodegenerative diseases such as Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) [8,15,16]. Cerebral ischemia, diabetes mellitus, cancer, autoimmune diseases, and other inflammatory-related issues have been discussed as potentially benefitting from resveratrol intervention [13,15,21,22]. Resveratrol provides protection from UV radiation explaining its potential use in the prevention of age-related macular degeneration (AMD) [23,24]. Potential mechanisms underlying resveratrol's actions are its ability to control protein activity via interaction with transmembrane and intracellular enzymes [25]
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