Homeostasis of intracellular

In a series of studies, Dubovsky et al. ( 34) measured intracellular calcium ion concentrations in bipolar manic and depressed patients. They found decreases in mean concentrations in four bipolar, manic, and five bipolar, depressed, patients, in comparison with seven normothymic subjects without personal or first-degree relative histories of psychiatric disorders. Their findings were consistent with a diffuse abnormality in the mechanisms modulating intracellular calcium homeostasis. Further, this phenomenon s presence in both platelets and lymphocytes lends credence to a disruption in the cell membrane, the G-protein, or other mechanisms involved in the homeostasis of intracellular calcium ion concentrations. This may also support an extension of their findings from peripheral to neuronal tissue. 

Because of their strategic localization, astrocytes play a crucial role in maintaining the extracellular ionic homeostasis, provide energetic metabolites to neurons and remove excess of neurotransmitter in schedule with synaptic activity. In addition, the strategic location of astrocytes allows them to carefully monitor and control the level of synaptic activity. Indeed, number of papers during the last 15 years have shown that cultured astrocytes can respond to a variety of neurotransmitters with a variety of different patterns of intracellular calcium increases (Verkhratsky et al. 1998). Later on, studies performed in intact tissue preparations (acute brain slices) further established that the plasma membrane receptors can sense external inputs (such as the spillover of neurotransmitters during intense synaptic activity) and transduce them as intracellular calcium elevations, mostly via release of calcium from internal stores (Dani et al. 1992 Murphy et al. 1993 Porter and McCarthy... 

A number of other members of the SLC9A family are thought to be involved in the reabsorption of Na+ and HC03 by the epithelia of the kidney and the gastrointestinal tract, while others seem to play a role in regulating the pH homeostasis in intracellular organelles. 

The Golgi apparatus also appears to be an important regulator of intracellular Ca2+ homeostasis. It has a SERCA pump, as well as an unusual Ca2+-ATPase that can transport Ca2+ and Mn2+ with high affinity for Ca2+ uptake. Ca2+ release is mediated by a channel that is modulated by InsP3, similar to that in the ER. However, it does not seem to have ryanodine-type channels. 

Several mechanisms have been postulated to account for thallium s toxicity, including ligand formation with sulfhydryl groups of enzymes and transport proteins, inhibition of cellular respiration, interaction with riboflavin and riboflavin-based cofactors, alteration of the activity of K -dependent proteins, and disruption of intracellular calcium homeostasis. ... 

Interference with any of these processes may be caused by toxic compounds and can alter calcium homeostasis. This can allow an influx of Ca2+, inhibition of export of Ca2+ out of the cell, or a release of Ca2+ from compartments within the cell. The result of each of these will be a rise of intracellular Ca2+, which can cause a variety of damaging events. 

The depletion of GSH and NADPH will allow the oxidation of protein sulfydryl groups, which may be an important step in the toxicity. Thus, GSH and protein sulfydryl groups, such as those on Ca2+-transporting proteins, are important for the maintenance of intracellular calcium homeostasis. Thus, paracetamol and NAPQI cause an increase in cytosolic calcium, and paracetamol inhibits the Na+/K+ ATPase pump in isolated hepatocytes. 

Insulin is a storage hormone produced by the pancreas. Insulin shuttles nutrients, such as carbohydrates, fats and amino acids (derived from proteins) into cells. The main function of insulin is to maintain homeostasis of circulatory glucose, and intracellular glycogen storage. It also aids in fat storage. 

Pereira C. F. M. and Resende de Oliveira C. (2000). Oxidative glutamate toxicity involves mitochondrial dysfunction and perturbation of intracellular Ca2+ homeostasis. Neurosci. Res. 37 227-236. 

Decrease in the ability of the heart to effectively contract is one of the major causes for the increased incidence of morbidity and mortality in diabetic patients (Rubier 1972). Both electrical and mechanical properties of the myocardium from diabetic patients may be significantly impaired, which has been attributed to alterations in intracellular Ca2+ homeostasis (Pierce 1983 Bouchard 1991 Yaras 2005). Weakened contractility of myocytes isolated from streptozotocin (STZ)-induced diabetic rats correlated with a reduced rate of the rise and decline of intracellular Ca2+ transients elicited by electrical stimulation (Choi 2002), which has been attributed to abnormal SR pump activity (Ganguly 1983), decreased SR Ca2+ storage (Bouchard 1991), and reduced Na+/Ca2+ exchanger activity (Yaras 2005). However,... 

Not only ionotropic receptors but also metabotropic receptors are associated with cutaneous barrier homeostasis. /32-adrenergic receptor antagonist prevented epidermal hyperplasia induced by barrier disruption.48 In the case of metabotropic receptors, the level of intracellular cAMP in the epidermal keratinocytes is associated with cutaneous barrier homeostasis and epidermal hyperplasia.49... 

The G-protein coupled receptors modulate intracellular cAMP level, which plays a crucial role in epidermal barrier homeostasis.5 Increase of intracellular cAMP in epidermal keratinocytes by topical application of forskolin delays barrier recovery, while cAMP antagonists accelerate the barrier recovery. Activation of dopamine 2-like receptors (manuscript in preparation), melatonin receptors, or serotonin receptor (type 5-HT1) decreases intracellular cAMP and consequently accelerates the barrier recovery (Figure 15.1), while activation of adrenergic 32 receptors increases intracellular cAMP and delays the barrier repair.6 Barrier disruption induces an increase of the intracellular cAMP level. Thus, topical application of agonists of receptors that reduce intracellular cAMP accelerates the barrier repair. Our results are summarized in Table. 15.1. 

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