Cellular death

Apoptosis is known as programmed cell death and represents also a control mechanism within the cell that reacts to the changes in its environment. This active cellular death process is characterized by distinctive morphological changes... 

DNA lesions is critical for cell survival, and errors in this process can lead not only to cellular death but to oncogenesis. 

Expression The sustained high calcium concentrations pave the way for destructive cascades causing neuronal degeneration. Phospholipase, proteases, and FRs are activated, degrading neuronal membranes and causing cellular death (Babu et al. 1994). 

The increase of intraneuronal calcium is related to degeneration and cellular death. Excitatory amino acids have been associated with calcium levels. In this sense, the blocking agents of the inflow of calcium to the neurons, which also produce a vasodilation, could have a therapeutic use in AD. Nimodipine, a dihydropyridine with a selective action on the vascular brain territory, has shown improvement in some psychometric batteries of patients with AD at 90-180 mg/day [Jarvik 1991]. However, more studies with this drug are needed. 

Previous studies have shown that muscle lysosomal hydrolases are released early in the postmortem period due to a decrease in intracellular ATP concentrations. The decreased intracellular ATP level causes the rupture of the lysosomal membrane (14), releasing hydrolytic enzymes (proteases, lipases, and glycosidases) that further potentiate the weakening of membrane integrity and cellular function. Furthermore, as the acidosis increases (due to the anaerobic conditions associated with cellular death) the intramuscular pH to levels reach that which are optimal for the activity of several lysosomal thiol proteinases. 

In this particular case, one F ion chelates two Ca or Mg ions so disrupting the biochemical metabolisms until the occurrence of cellular death and the necrosis of tissues. It is a movement of physiological balance. This mechanism explains the first historic reflex to strengthen the contributions in ions Ca or Mg ions to answer the need of chelation of the fluoride ion. This resulted,... 

The identity of factors released from damaged neurons to signal microglial cell activation may depend upon which type of neural cell is damaged, neuron versus glial, and on the the toxin or stimulus, glutamate versus /1-amyloid versus a-synuclein, and the nature of cellular death, apoptosis versus necrosis. Similarly, the molecular mechanisms and internal and external factors that modulate the dynamic aspects of acute and chronic inflammation in cell injury mediated by glutamate remain unclear. It also remains unclear to what extent inflammation is beneficial... 

Because they are easily accessible, glycans displayed on the surface of mammalian cells provide enormous opportunities to bind to many microbial pathogens, ranging from viruses to molecular toxins and from pathogenic bacteria to parasites. In multivalent binding, multiple interactions between ligands and various receptors are common (Fig. 16.1). One representative example is ricin—a versatile and durable A-B-type toxin—in which one of the protein chains (the B chain) is a lectin that interacts and binds terminal galactose (Gal) on the surface of eukaryotic cells with multivalent interactions to facilitate entry of the other peptide chain (the A chain) into the cell to cause cellular death via the catalytic... 

Until now the exact mechanism of cellular death induced by Ti02 is unknown. Nevertheless it seems obvious that incorporation of Ti02 particles into cells should... 

A phytotoxin may require binding sites within a plant in order to affect it adversely (1, 14). In the case of maculosin, a host specific toxin, a very specific receptor site may exist in spotted knapweed. Such a site may be a protein that has a normal role in the maintenance of cellular function, but coincidentally serves as a phytotoxin receptor (li, 15). Binding of the toxin by the receptor may result in a disruption in the functional role of the protein or result in a cascade effect involving other proteins. Either effect could result in cellular death (1, 111. 

Inhibition of ceramide synthase could cause symptoms by depletion of ceramide and ceramide derivatives or by toxic increases in sphinganine and its derivatives. The effects of these phytotoxins are so rapid, that it is unlikely that depletion of ceramides is responsible for cellular death. Others have invoked induction of apoptosis in the mode of action of these compounds [e.g., 6] however, treatment of plant tissues with phytoshingosine and sphinganine causes symptoms very similar to those caused by inhibition of ceramide synthase [7]. Very low levels of AAL-toxin tuid other ceramide synthase inhibitiors may cause apoptosis, but the rapidity of plasma membrtme damage at one micromolar and higher concentrations makes it unlikely that it is involved in the main phytotoxic effect. Attempts have been made to find a ceramide synthase inhibitor with good phytotoxicity, but little mammalitm toxicity [e.g., 8]. However, even inhibitors with little structural similarity to the fumonisins such as australifimgin [9], have relatively little difference between mammalian and plant toxicity. Nevertheless, these studies demonstrate that the ceramide synthase pathway is a viable site for herbicides, provided an inhibitor can be found that is plant specific. This topic is considered in more detail in a recent review [10]. 

Initiation of apoptosis includes several alternative (or, at least, independent) mechanisms. The cell makes a conclusion about preferable mode of cellular death choosing between variety of factors, the level of ROS being only one of them. In fact, not the ROS level itself but an inability of cellular defense system to resist their unfavorable effects results in decision to dye. 

Figure 7 demonstrates excitotoxic effect of NMDA on neuron suspension. Exposure of the cells to 2 mM NMDA for 3 hrs results in cellular death by both necrosis and apoptosis. It is also seen that light necrosis in a control sample (Figure 7A) is substituted by heavy necrosis (Figure 7B). Lower concentration of this and other glutamate agonists exposed to the cells for a shorter time results in apoptosis not affecting amount of necrotic cells the earliest features of apoptosis appeared 1-3 hrs after beginning of the experiment.

Amyotrophic lateral sclerosis is an adult onset neurodegenerative disease. The motomeurons in the brainstem and in the spinal cord are selectively damaged. 15-20% of the patients have a mutation in the gene for the cytosolic superoxide dismutase (SOD I). It is thought that superoxide is not detoxified, side reactions of this enzyme form oxidants including peroxynitrite and the formation of nitrated proteins, is one of the reasons for cellular death [5]. 

The specific rate of cellular death, k, is defined as the number of dying cells per unit (e.g. billion) of living cells present in the culture medium per unit time (e.g. hour). 

Phase 2 is from 40 to 140 h, where all the specific rates progressively decrease except the cellular death rate, which continues to rise. This reduction in the specific rates of growth and metabolism is mainly due to glutamine limitation. However, the accumulation of lactate and ammonia may also have a kinetic... 

The kinetic expression for the specific rate of cellular death (Equation 4.3.18) contains three terms that each express a possible increase of the specific death rate and can be evaluated as follows ... 

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