Ion homeostasis

The disruption of C1C-2 in mice leads to male infertility, blindness, and leukodystrophy, and was attributed to defective extracellular ion homeostasis in narrow clefts. C1C-2 yields currents that slowly activate upon hyperpolarization. It is also activated by cell swelling and by extracellular acidification. Structural determinants that are essential for these types of activation were identified by mutagenesis. There is a report that C1C-2 might be mutated in human epilepsy, but this has not been confirmed in fiuther studies. 

HIV proteins can also disrupt ion homeostasis in astrocytes, which compromises neuronal function (Pulliam et al. 1993 Benos et al. 1994a, b Holden et al. 1999). Intact HIV-1 virions or gpl20 also markedly inhibit glutamate uptake by astrocytes and cause reductions in excitatory amino acid transporter-2 (EAAT2) mRNA and protein levels (Wang et al. 2003). The inability of astrocytes to buffer extracellular glutamate is likely to decrease the excitotoxic threshold of bystander neurons. 

Maintenance of organellar integrity Maintenance of ATP levels Maintenance of ion homeostasis Membrane surface blebbing Nuclear chromatin condensation/fragmentation Requires synthesis of death effector proteins Prevented by blocking steps in the death cascade Does not adversely affect neighbor cells... 

Organellar swelling and damage Depletion of ATP Loss of ion homeostasis Membrane rupture Nuclear lysis... 

Necrosis is a dramatic and very rapid form of cell death in which essentially every compartment of the cell disintegrates. Necrosis is characterized by marked dysregulation of ion homeostasis resulting in cell swelling, dilation of mitochondria and the ER and the formation of vacuoles in the cytoplasm [33], Proteases play important roles in the degradation of cells during necrosis. In contrast to apoptosis, where caspases are the key death proteases, calpains and lysosomal proteases (cathepsins B and D, in particular) are major players in necrosis. Caspases may be activated in response to mitochondrial damage and... 

In regards to necrosis, it is clear that the old adage an ounce of prevention is worth a pound of cure applies. Agents that stabilize ion homeostasis have proved to be effective in preventing necrosis in cell culture studies. For example, drugs that activate plasma membrane potassium ion channels or chloride ion channels can prevent membrane depolarization and so inhibit sodium and calcium ion influx. Agents that prevent large sustained increases in intracellular free calcium levels can also prevent neuronal... 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

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. 

As in Chapter 7, we successively consider the transport, storage and metal ion homeostasis in prokaryotes, plants and animals. Since the assimilation of metals in unicellular bacteria does not require their transport to other cell types, we confine our discussion only to storage and homeostasis. 

Biochemical features Loss of ion homeostasis Random digestion of DNA causing smear of DNA after agarose gel electrophoresis... 

Mulet JM, Leube MP, Kron SJ, Rios G, Fink GR, Serrano R (1999) A novel mechanism of ion homeostasis and salt tolerance in yeast the Hal4 and Hal5 protein kinases modulate the Trkl-Trk2 potassium transporter. Mol Cell Biol 19 3328-3337... 

Flood A, Headrick JP (2001) Functional characterization of coronary vascular adenosine receptors in the mouse. Br J Pharmacol 133(7) 1063-1072 Fralix TA, Murphy E, London RE, Steenbergen C (1993) Protective effects of adenosine in the perfused rat heart changes in metabolism and intracellular ion homeostasis. Am J Physiol 264(4 Pt 1) C986-C994... 

Mark R. J., Lovell M. A., Markesbery W. R., Uchida K., and Mattson M. R (1997). A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid /3-peptide. J. Neurochem. 68 255-264. 

Haploinsufficiency of human SPCA1 results in Hailey-Hailey disease (HHD) (Hu et al., 2000 Sudbrak et al., 2000), which highlights the critical role of this housekeeping Ca2+ and Mn2+ pump in cellular ion homeostasis. We will review the properties of this mutated SPCA1 and discuss how SPCA1 contributes to the physiology of the normal skin. 

Due to its unique catalytic properties and restricted expression pattern, SPCA2 must have a special role to play in cellular ion homeostasis, a role which should be further investigated. 

PTH is a naturally occurring polypeptide with 84 amino acid residues that acts as the major regulator of calcium ion homeostasis [68]. The first two amino acids of PTH from the amino N-terminus are required for biological activity. Proteolytic fragments of PTH are inactive at the PTH-1 receptor, but may cross-react with an IA. The putative peptide PTH (7-84) fragment was reported to exist at 10- to 20-fold higher concentrations than the intact PTH (1-84), depending upon health status [69]. 

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