Calcium overload

Kruman 11, Nath A, Mattson MP (1998) HlV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp Neurol 154(2) 276-288... 

In experiments using oxidant stress induced by the photoactivation of rose bengal (10 nM), a 75% decline in the calcium inward current was observed after 10 min, with only a sUght acceleration in the inactivation kinetics of the current (Shattock etal., 1990). However, this decline in the calcium inward current appears to occur secondary to an oxidant stress-induced calcium overload and not as... 

Recent studies by Crompton et al. have shown that oxidant stress may open a Ca-sensitive, non-selective pore in the inner mitochondrial membrane that is blocked by cyclosporin A (Crompton, 1990 Crompton and Costi, 1990). This pore opening results in massive mitochondrial swelling, dissipation of the transmembrane proton gradient and disruption of mitochondrial energy production (Crompton et al., 1992). Since mitochondria may play a role as a slow, high-capacity cytosolic calcium buffer (Isenberg et al., 1993), disruption of mitochondrial function may also contribute to calcium overload and cell injury. 

Coetzee and Opie (1988, 1992) have suggested that the cellular calcium overload induced by oxidant stress is mediated by an increase in calcium influx through the L-type calcium channel. However, a number of other studies, using different radical-generating systems, experimental conditions and species, have described no significant effects on the calcium channel over the period of exposure necessary to induce cellular calcium overload (Bhatnagar etal., 1990 Shattock etal., 1990 Beresewicz... 

Matsuura, H., Shattock, M.J. and Hearse, D.J. (1991). Calcium overload induced by oxidant stress is dependent on an intact transarcolemmal sodium gradient. J. Mol. Cell. Cardiol. 23, S7. 

Chiueh, C.C., Miyake, J., Peng, M.T. Role of dopamine autoxidation, hydroxyl radical generation, and calcium overload in underlying mechanisms involved in MPTP-induced parkinsonism. Adv. Neurol. 60 251, 1993. 

The functions of mtNOS in mitochondria have been studied (see Chapter 23). Ghafourifar et al. [177] found that the calcium-induced stimulation of mtNOS caused the release of cytochrome c from mitochondria and induced apoptosis. On the other hand, the same group of authors [178] showed that the production of NO by mtNOS and superoxide in mitochondria resulted in the formation of peroxynitrite and stimulated calcium release, indicating the existence of a feedback loop which prevents calcium overload in mitochondria. 

Chelators of transition metals, mainly iron and copper, are usually considered as antioxidants because of their ability to inhibit free radical-mediated damaging processes. Actually, the so-called chelating therapy has been in the use probably even earlier than antioxidant therapy because it is an obvious pathway to treat the development of pathologies depending on metal overload (such as calcium overload in atherosclerosis or iron overload in thalassemia) with compounds capable of removing metals from an organism. Understanding of chelators as antioxidants came later when much attention was drawn to the possibility of in vivo hydroxyl radical formation via the Fenton reaction ... 

The mechanism of action of ranolazine has not been determined, but it may be related to reduction in calcium overload in ischemic myocytes through inhibition of the late sodium current. Its antianginal effects do not depend on reductions in HR or blood pressure. 

Digitalis glycosides enhance the inotropic state by increasing the intracellular calcium concentration. Intracellular calcium overload is also the mechanism for proarrhythmia associated with digitalis intoxication. The direct effect of digitalis on the electrophysiology of the myocytes is to increase the slope of phase 4 depolarization, an effect that enhances automaticity. 

Rumbrin (181) from the fungus Auxarthron umbrinum exhibits cytoprotective activity against cell death caused by calcium overload in 3T3-Swiss albino cells. It also shows inhibitory activity against lipid peroxidation in rat brain homogenate and low intraperitoneal toxicity in mice [142]. 

Barnea, E., Zuk, D., Simantov, R., Nudel, U., and Yaffe, D., 1990, Specificity of expression of the muscle and brain dystrophin gene promoters in muscle and brain cells, Neuron, 5, pp 881-888. Basset, O., Boittin, F.X., Cognard, C., Constantin, B., and Ruegg, U.T., 2006, Bcl-2 overexpression prevents calcium overload and subsequent apoptosis in dystrophic myotubes, Biochem J, 395, pp 267-276. 

The occurrence of the proteolytic activity of calpain confirms that abnormal glutamate overactivates the NMDA receptor leading to intracellular calcium overload. Neuroprotection afforded by calpain inhibitors lends further support to the role of glutamate in RGC degeneration (Oka et al., 2006 Sakamoto et al., 2000). 

Noble, D. and Noble, P. J. Late sodium current in the pathophysiology of cardiovascular disease consequences of sodium-calcium overload. Heart 2006, 92 ivl-iv5. Noble, D. and Varghese, A. Modeling of sodium-calcium overload arrhythmias and... 

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