Calcium homeostasis, disturbances

Several studies investigated the possible role of calcium homeostasis disturbances in OPIDP pathogenesis, but results were inconsistent across various OPs and species (Suwita et al, 1986 El-Fawal et al, 1989 Luttrell et al., 1993 Barber et al, 2001 Piao el al, 2003 Wu et al, 2003 Choudhary and Gill, 2001),... 

Many types of liver injury are caused by a number of biochemical reactions of toxicants or their active metabolites. Such reactions inclnde covalent binding, lipid peroxidation, inhibition of protein synthesis, pertnrbation of calcium homeostasis, disturbance of biliary prodnction, and a variety of immunologic reactions. The types of liver injury from such biochemical reactions include steatosis (fatty liver), liver necrosis, cirrhosis, cholestasis, hepatitis, and carcinogenesis. The toxicants that cause these injuries are discussed in brief. 

There is evidence for immunosuppressive effects of PAHs in rodents (Davila et al. 1997). For example, strong immunosuppressive effects were reported in mice that had been dosed with benzo[fl]pyrene and 3-methyl cholanthrene, effects that persisted for up to 18 months (Environmental Health Criteria 202). Multiple immu-notoxic effects have been reported in rodents, and there is evidence that these result from disturbance of calcium homeostasis (Davila et al. 1997). PAHs can activate protein tyrosine kinases in T cells that initiate the activation of a form of phospholipase C. Consequently, release of inositol triphosphate—a molecule that immobilizes Ca + from storage pools in the endoplasmic reticulum—is enhanced. 

The above studies have generated a huge body of invaluable data concerning the effects of oxidative stress on cells. In particular the importance of GSH in cell protection and the role of disturbed calcium homeostasis in cell killing have been greatly illuminated. 

In this review, we consider the evidence that disturbances in calcium triggered by Ap may contribute to the synaptic loss in human AD. Furthermore, we discuss the likelihood that calcium dyshomeostasis in AD, and AD mouse models, may contribute to memory impairments. We have not discussed the role of the presenilins in calcium homeostasis as they have recently been reviewed (LaFerla, 2002 Smith... 

Chronic disturbances in calcium homeostasis can also produce problems in bone calcification. Likewise, various metabolic bone diseases can alter blood calcium levels, leading to hypocalcemia or hypercalcemia. Some of the more common metabolic diseases... 

Ricin disturbed calcium homeostasis leading to cell necrosis. 

Mechanism and susceptibility factors The mechanism of cisplatin-induced neurotoxicity has not been fully explained. Cisplatin appears to affect neurons in the dorsal root ganglia. It has also been suggested that it can act as a calcium channel blocker, altering intracellular calcium homeostasis and leading to apoptosis of exposed neurons, such as those of the dorsal root ganglia. Cisplatin-induced sensory neuropathy is predominantly characterized by symptoms such as numbness and tingling, paresthesia of the upper and lower extremities, reduced deep-tendon reflexes, and leg weakness with gait disturbance. The first symptoms are often observed after a cumulative dose of 300-600 mg/m. Risk factors include diabetes mellitus, alcohol consumption, or inherited neuropathies. Advanced age has not been identified as an independent risk factor when there is no co-morbidity (67-70). 

Disturbance of the intracellular calcium homeostasis is involved in the pathogenesis of neurodegeneration and probably in the extracellular accumulation of Ap. Calcium channel blockade attenuates Ap-induced neuronal damage. Several calcium channel blockers have been tested in dementia with poor results. In some clinical trials, nimodipine and nilvadipine showed some positive results on cognition, whereas other calcium channel blockers failed [515]. 

It is an attractive concept that the uniformity of the plasma calcium concentration in health is attained through balanced low levels of secretion of both parathormone and thyrocalcitonin, and that disturbances of calcium homeostasis may result both in a reduction of the resting level of secretion of one hormone, and in a raised output of the other. Until both hormones can be assayed with precision, the possibility of such a dual mechanism, operating at physiological levels of plasma calcium variation, must remain somewhat speculative. 

Disturbances of calcium homeostasis have often been reported in diseases involving abnormal secretion of thyroid hormone. In thyrotoxicosis (G5, K2) the disturbance, if present, usually manifests itself as hypercalcemia of moderate degree, with loss of calcium from the bones and increased urinary output of calcium, thus suggesting a possible deficiency of thyrocalcitonin output in this type of thyroid disease. Most such observations antedate the discovery of thyrocalcitonin, and there is not yet much information on the response of such patients to an... 

Altered calcium homeostasis also may play an important role in the pathogenesis of hypertension. A lack of dietary calcium hypothetically can disturb the balance between intracellular and extracellular calcium, resulting in an increased intracellular calcium concentration. This imbalance can alter vascular smooth muscle function by increasing peripheral vascular resistance. Some studies have shown that dietary calcium supplementation results in a modest BP reduction in hypertensive patients. 

By reducing the dose of calcitriol below 0.1 (j,g/kg/day in order to limit disturbance of calcium homeostasis, the immunosuppressive activity also diminished. Thus, ZK... 

Vitamin D is required for efficient absorption of calcium and phosphorus in the intestinal trad, and it is also necessary for calcium and phosphorus homeostasis within the body. Deficiency of vitamin D will, therefore, lead to calcium deficiency and will affect processes such as bone formation and egg-shell production. Bone mineralisation is dependent on the maintenance of Gi and phosphate levels. The effect of vitamin D on these processes is mediated by calbindin and is discussed in Section 10.6. Aluminium toxicity is, at least in part, accounted for by disturbance of calcium homeostasis. Aluminium compounds reduce vitamin D-dependent Gi absorption in chicks. They act by reducing the intestinal calbindin concentration (Dunn et al, 1993). 

Jewell, S.A., Bellomo, G., Thor, H., Orrenius, S. and Smith, M.T. (1982). Bleb formation in hepatocytes during drug metabolism is caused by disturbances in thiol and calcium ion homeostasis. Science 217 1257-1258. 

Calcium and phosphate, the major mineral constituents of bone, are also two of the most important minerals for general cellular function. Accordingly, the body has evolved a complex set of mechanisms by which calcium and phosphate homeostasis are carefully maintained (Figure 42-1). Approximately 98% of the 1-2 kg of calcium and 85% of the 1 kg of phosphorus in the human adult are found in bone, the principal reservoir for these minerals. These functions are dynamic, with constant remodeling of bone and ready exchange of bone mineral with that in the extracellular fluid. Bone also serves as the principal structural support for the body and provides the space for hematopoiesis. Thus, abnormalities in bone mineral homeostasis can lead not only to a wide variety of cellular dysfunctions (eg, tetany, coma, muscle weakness) but also to disturbances in structural support of the body (eg, osteoporosis with fractures) and loss of hematopoietic capacity (eg, infantile osteopetrosis). 

Perheentupa J. Disturbed calcium and phosphate homeostasis during treatment with ACTH of infantile spasms. Arch Dis Child 1986 61(7) 671-6. 

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