Brain distribution subcellular localization

While the abundance of DBT does not oscillate, the subcellular localization of DBT does change throughout the circadian day (Fig. 2). In Drosophila, the subcellular distribution of DBT in the lateral neurons of the brain and in photoreceptor cells of the eye largely follows the changing localization of PER (Kloss et al 2001). In mammals, the pattern of CKl accumulation is also under circadian control the kinase appears to associate initially with mPER and mCRY in the cytoplasm, but it is also found in nuclear complexes and may regulate their movement to the nucleus (Lee et al 2001). 

Villanueva, S. and Steward, 0. (2001) Protein synthesis at the synapse developmental changes, subcellular localization and regional distribution of polypeptides synthesized in isolated dendritic fragments. Brain Res. Mol. Brain Res. 91, 148-153. 

Since protection against radical damage during the rapid metabolic rates encountered in development and maturation is almost certainly critical, several workers have focused on the subcellular localization and distribution of enzymes that serve this purpose, especially in the brain. Those determined by Del Maestro and McDonald [493,494] include superoxide... 

The action of catecholamines released at the synapse is modulated by diffusion and reuptake into presynaptic nerve terminals. Catecholamines diffuse from the site of release, interact with receptors and are transported back into the nerve terminal. Some of the catecholamine molecules may be catabolized by MAO and COMT. The cate-cholamine-reuptake process was originally described by Axelrod [18]. He observed that, when radioactive norepinephrine was injected intravenously, it accumulated in tissues in direct proportion to the density of the sympathetic innervation in the tissue. The amine taken up into the tissues was protected from catabolic degradation, and studies of the subcellular distribution of catecholamines showed that they were localized to synaptic vesicles. Ablation of the sympathetic input to organs abolished the ability of vesicles to accumulate and store radioactive norepinephrine. Subsequent studies demonstrated that this Na+- and Cl -dependent uptake process is a characteristic feature of catecholamine-containing neurons in both the periphery and the brain (Table 12-2). 

Subcellular distribution of tilorone hydrochloride has been examined. Gaur and Chandra24 studied the subcellular distribution of radioactivity in liver, spleen, brain, lungs and kidney of mice and liver, spleen, brain, kidney and heart of rats after a dose of 50 mg/kg of 14C-tilorone by intraperitoneal injection. A substantial proportion of the radioactivity was found in the fraction which sediments at 700 x g and contains, in addition to cell debris, the nuclei. The remaining radioactivity was distributed between the mitochondrial, microsomal and supernatant fractions. The authors suggested that the primary target of tilorone hydrochloride may indeed be the molecular species localized in the nuclei i.e., the DNA. 

Enkephalinase distribution is wide-spread in the brain and peripheral organs and soluble forms are present in human plasma and cerebrospinal fluid. In the central nervous system, its distribution largely parallels regional distribution of the enkephalins and opioid receptors (striatum > cortex > cerebellum) and it is localized in the particulate fraction of brain homogenates [26,50] in a non-xmiform fashion in mice, rats and humans. In the cortex or the striatum, opioid receptors and the enzyme display a parallel subcellular distribution pattern. Both enkephalinase and opioid receptors are present on the membranes from nerve-terminal regions, suggesting their involvement in synaptic transmission. 

The subcellular distribution of ThTP in animal cells varies with the tissue studied. In rodent brain, it is mainly localized in mitochondria, while it is mostly cytoplasmic in skeletal muscle. Those differences are probably related to different mechanisms of ThTP synthesis (see below). 

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