Ischemia second messengers

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

Heart muscle fibers are coupled by gap junctions. These intercellular channels provide the exchange of small molecules (<1,000 D), like second messengers, between the cells and they allow electrical coupling. Thus, these cells connected to each other form a syncytium. However, from mapping studies it became evident that under certain conditions, e.g. regional ischemia, the ischemic region uncouples. In addition, mapping studies demonstrated that there is a special activation pattern which accounts for a directed activation of the whole heart. This activation pattern exhibits a considerable similarity from beat to beat. It is well known that the conduction velocity varies between... 

Neurotransmitters such as glutamate interact with a variety of receptors that are coupled to second messenger systems. The effects of mild hypothermia on ischemia-induced changes in intracellular messenger systems and mediators have also been studied and are described in Chapter 2. 

Stress stimuli come in a variety of forms, such as deprivation of trophic factors, ionizing radiation, free radicals (e.g., peroxynitrite), hypoxia, ischemia, heat shock, lipid second messengers (such as ceramide) (Singh et al., 1998), TNF-a, or Fas-ligand. In the brain, neurons are especially susceptible to stress stimuli these stimuli lead to activation of intracellular pathways that either promote apoptosis or defense-adaptation mechanisms. At least three such pathways have been well studied. These pathways lead to the activation of c-Jun N-terminal kinases (JNKs), p38 kinases. 

Koh JY, Suh SW, Gwag BJ, He YY, Hsu CY, Choi DW (1996) The role of zinc in selective neuronal death after transient global cerebral ischemia. Science 272 1013-1016 Koo EH, Squazzo SL (1994) Evidence that production and release of eimyloid beta-protein involves the endocytic pathway. J Biol Chem 269 17386-17389 Korichneva I, Hoyos B, Chua R, Levi E, HammerUng U (2002) Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen. J Biol Chem 277 44327 4331... 

Second messengers in gerbil brsin Global Ischemia... 

Excitable membranes maintain and rapidly modulate substantial transmembrane ion gradients in response to stimuli 576 Specific lipid messengers are cleaved from reservoir phospholipids by phospholipases upon activation by various stimuli 576 Phospholipids in synaptic membranes are an important target in seizures, head injury, neurodegenerative diseases and cerebral ischemia 576 Some molecular species of phospholipids in excitable membranes are reservoirs of bioactive lipids that act as messengers 576 Mammalian phospholipids generally contain polyunsaturated fatty acyl chains almost exclusively esterified to the second carbon of glycerol 577... 

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