Cellular repair mechanism

Ischemic brain injury results in the death of distinct susceptible populations of neurons in the brain. In addition, the injury concurrently triggers cellular repair mechanisms. SVZ precursors can be recruited following transient middle cerebral artery occlusion (Jin et al., 2001 Zhang et al., 2001). In this stroke... 

It is apparent that a variety of factors, acting singly or as multiple stressors, can contribute to UV-induced injury in freshwater organisms. Each species of freshwater organism will be susceptible to harmful levels of solar UVR depending on the conditions present at a certain point in time. If conditions are appropriate for UVR to penetrate sensitive cellular molecules, and if cellular repair mechanisms are unable to keep up with the rate of cellular damage, UV-induced injury is inevitable. 

Interaction with DNA replication and cellular repair mechanisms. 

The DNA crosslinks formed by cis-DDP interfere with DNA replication and eventually cause cell death. The activity of DNA polymerases is impaired by DNA-platinum adducts (54-56). Furthermore, although the cell is capable of repairing DNA-platinum adducts (50,57-59), the intrastrand DNA crosslinks produced by cis-DDP do not cause large distortions of the double helix and so may not be easily recognized and repaired (51,60,61). Despite cellular repair mechanisms, a sufficient concentration of cis-DDP will inhibit replication and prevent cell division (20-23,62-64). In some cells, cis-DDP appears to also impair the cell s ability to transcribe genes needed for mitosis (63,64), and even cells which manage to divide initially after cis-DDP treatment often do not display long-term survival (22,23). 

One important point of controversy in risk extrapolation is the existence of the threshold level for carcinogenic and mutagenic response to a pollutant. Some argue that an organism is able to cope with low doses of a substance through metabolic processes or repair mechanisms, so that harmful effects do not appear until a certain minimum threshold, or "safe dose", is surpassed. Others contend that a carcinogenic substance must be considered potentially harmful at any dose, and that even a single molecule may initiate a tumor at the cellular level. This is the so-called "one-hit" hypothesis. 

Conversion of epoxides (arene oxides) into phenols is spontaneous. The conversion of epoxides into dihydrodiols is catalyzed by EH (EC 4.2.1.63). Hydroxyl containing PAHs can act as substrates for conjugases (C) (UDP glucuronsyl transferase (EC 2.4.1.17) and phenol sulphotransferase (EC 2.8.2.1)). This pathway usually leads to inactive excretable products. Epoxides are scavenged by GSH and the reaction is catalyzed by GSHt (EC 2.5.1.18). When GSH is depleted and/or the other pathways are saturated, epoxides of dihydrodiols (particularly 7,8-diol-9,10-epoxides in the case of BP) and phenol metabolites react with cellular macromolecules such as DNA, RNA, and protein. If repair mechanisms are exceeded the detrimental effects of PAH may result. 

Heat-shock protein is part of a repair mechanism which involves protection and repair of cells following cellular damage due to exposure to a wide variety of stressors. Heat-shock stress protein HSP 70 has the capability to restore the damaged proteins under adverse conditions. Significant increases in the H S P 70 may directly interfere with ongoing cellular processes or may alter the function of the cells, whereas alowto... 

It is assumed that for health effects other than cancer, a threshold or non-linear dose-response relationship exists. This is based on known compensatory and adaptive mechanisms that protect against the toxic effects of childhood exposures, as well as on repair mechanisms at the molecular, cellular, and tissue... 

The neuroprotective properties of mild hypothermia have been demonstrated in numerous experimental animal models. Research in this area has been conducted for many years, yet the mechanisms of cerebral protection by mild hypothermia remain unclear and continue to be the subject of intense investigation. The neuroprotective effects of mild hypothermia have been attributed to alterations in metabolic rate (24), neurotransmitter release (25-27), activity of protein kinases (28), resynthesis of cellular repair proteins (29), cerebral blood flow (30), preservation of the blood-brain barrier (BBB) (31), attenuation of inflammatory processes (32,33), and decreases in free radical production (34). Although these may all be components of a complex cascade leading to neurologic injury, it has become increasingly clear that the primary mechanism of action of hypothermia may be different at various temperatures as well as under different ischemic and traumatic conditions. 

Although research in this area has been conducted for more than 40 yr, the mechanisms of cerebral protection by mild hypothermia remain unclear and are still a source of controversy. Proposed mechanisms of neuroprotection by mild hypothermia include suppression of neurotransmitter release (2,3), reduced free radical production (4), activity of protein kinases (5), resynthesis of cellular repair proteins (6),... 

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