Toxic effects of metals: modulation of intracellular calcium homeostasis

Abstract

Metals and metalloids with their organic derivatives are part of the environment occurring naturally or being introduced upon human activity (e.g. industry, agriculture or medicine). Even if they are useful for humans, these chemicals could be highly toxic (e.g. mercury, lead, arsenic, tin) acting as neurotoxins or carcinogens. Several human cases of metal derived intoxication have been documented resulting in health complications or ending with death. The mechanisms of toxicity are not well understood. Since calcium is a universal second messenger in all cell types it is a good candidate to investigate how changes in the intracellular calcium homeostasis are involved in metal(loid) toxicity. In this mini-overview the interaction of metallic species with channel proteins at the outer cell membrane, as well as with calcium release sides from the calcium stores and the impairment with calcium extrusion mechanism is discussed.

IP3 receptor antagonist, 2‐APB, attenuates cisplatin induced Ca2+‐influx in HeLa‐S3 cells and prevents activation of calpain and induction of apoptosis

“…It has been demonstrated that intracellular calcium ([Ca 2+ ] i ) signals are involved in a number of events, including apoptotic pathways ( Mandic et al ., 2002 ; Arany et al ., 2004 ; Jaffe, 2005 ). While Ca 2+ could be released from the [Ca 2+ ] i stores, as it has been demonstrated for other metal compounds, such as trimethyltin or As 2 O 3 ( Florea and Büsselberg, 2005 , 2006 ; Florea et al ., 2005a , 2005b , 2007 ), Ca 2+ also could enter from the extracellular space through membrane channels. Recently it has been shown that the activation of inositol‐1,4,5‐trisphosphate (IP 3 ) receptors, found at the cellular membrane, results in an elevation of [Ca 2+ ] i ( Dellis et al ., 2006 ).…”

Crotonaldehyde induces apoptosis in alveolar macrophages through intracellular calcium, mitochondria and p53 signaling pathways

“…The imbalance of intracellular calcium homeostasis commonly leads to cellular apoptosis (Florea and Büsselberg, 2005). Accumulating data has reported that ROS can lead to the overload of Ca 2+ concentration in cells (Soliman et al, 2009).…”

Erythrocytes as a Model for Heavy Metal-Related Vascular Dysfunction: The Protective Effect of Dietary Components

“…Mercury toxicity is also associated with an increase in intracellular Ca 2+ due to both an increase in the influx of Ca 2+ from the extracellular environment and an increase in the mobilization of intracellular reserves [ 60 ]. This effect on calcium homeostasis, associated with the effect of calcium increase due to OS, is responsible for the activation of proteases, lipases, and endonucleases.…”