Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous studies on the local rate of energy metabolism of various brain regions during development and following experimental manipulation have been conducted using 2-deoxyglucose uptake and cytochrome oxidase (CO) histochemistry, both considered to be reliable indicators of long-term and short-term alterations in neuronal activity, respectively. Another method which has been related to neuronal activity is neuron-specific enolase (NSE) immunohistochemistry. An isoenzyme of enolase, a key element in the glycolytic pathway, NSE is present in neurons and neural-related cells e.g. neuroendocrine cells, pituicytes, and many tumor cells, but not in glia. The distribution on adjacent tissue sections of immunoreactive NSE and histochemically determined CO were mapped in the rat mesencephalon and adrenal medulla. Both methods showed highly restricted localization of staining which coincided with few exceptions in the most reactive areas, namely the superior colliculus, medial and lateral geniculate nuclei, red nucleus, lateral mammillary nucleus, interpeduncular nucleus and substantia nigra pars lateralis and pars reticulata. Immunoreactivity of varying intensity for NSE was also observed in perikarya and in processes of numerous scattered neurons throughout the mesencephalon, including the substantia nigra pars compacta, and reticular formation. The general correspondence in staining patterns between CO and NSE in the midbrain, supports the utility of NSE as a useful index of metabolic activity in neurons.
 ...
PMID:Neuron-specific enolase reflects metabolic activity in mesencephalic neurons of the rat. 131 69

The present study has examined certain metabolic markers in fetal neocortical tissue transplanted to the cortex, hippocampus, striatum, or ventricle. Particularly, the immunocytochemical expression of neuron-specific enolase (NSE) was studied in a series of host rats ranging between 10 days and 15 months postoperative. NSE is a major glycolytic pathway enzyme found in all neurons. The antibody to NSE is a very reliable marker for neuronal functional metabolic activity and developmental status and its onset has been shown to coincide with synaptic connections. In some grafts oxidative metabolic status was investigated using cytochrome oxidase (CO) histochemistry. In addition, the normal development of NSE expression in rat neocortex was also examined. In normal development, NSE was weakly expressed in fetal brain, but by 1-2 weeks postnatal the enzyme was strongly expressed in all neurons. Typical cortical laminar patterns were evident at 30 days with neurons in layer V and scattered interneurons the most strongly stained. In cortex-cortex transplants NSE expression was very weak; at 1-3 weeks postoperative, it was practically nonexistent; and at all later times only a minority of neurons had normal expression when compared to that in normal development even though by Nissl staining standards in adjacent sections they appeared "normal." Labeling indices ranged between 30 and 49%. Intraventricular grafts had consistently low NSE expression with labeling indices ranging between 18 and 46%. However, when the neocortical tissue was placed in other regions, neuronal NSE appeared only slightly below normal. CO histochemistry corroborated the NSE activity with regards to graft placement. Several possibilities that may account for reduced NSE profile in transplanted neurons include incomplete migration patterns, reduced synaptic connectivity, and potential ischemia causing lowered protein synthesis during reestablishment of vascular connections. If neuronal glycolysis is weakened, it is possible that neurotransmitter production or axonal transport are reduced. Since most energy capacity in brain is dependent on the glycolytic sequence for oxidative metabolism, reduced glycolytic capacity, as depicted by NSE expression, may suggest the presence of transplanted neurons that have adapted to their new environment with a relatively immature profile.
 ...
PMID:Developmental expression of neuron-specific enolase immunoreactivity and cytochrome oxidase activity in neocortical transplants. 828 24

Apolipoprotein (apo) E4 is the major genetic risk factor for late-onset Alzheimer disease (AD). ApoE4 assumes a pathological conformation through an intramolecular interaction mediated by Arg-61 in the amino-terminal domain and Glu-255 in the carboxyl-terminal domain, referred to as apoE4 domain interaction. Because AD is associated with mitochondrial dysfunction, we examined the effect of apoE4 domain interaction on mitochondrial respiratory function. Steady-state amounts of mitochondrial respiratory complexes were examined in neurons cultured from brain cortices of neuron-specific enolase promoter-driven apoE3 (NSE-apoE3) or apoE4 (NSE-apoE4) transgenic mice. All subunits of mitochondrial respiratory complexes assessed were significantly lower in NSE-apoE4 neurons compared with NSE-apoE3 neurons. However, no significant differences in levels of mitochondrial complexes were detected between astrocytes expressing different apoE isoforms driven by the glial fibrillary acidic protein promoter, leading to our conclusion that the effect of apoE4 is neuron specific. In neuroblastoma Neuro-2A (N2A) cells, apoE4 expression reduced the levels of mitochondrial respiratory complexes I, IV, and V. Complex IV enzymatic activity was also decreased, lowering mitochondrial respiratory capacity. Mutant apoE4 (apoE4-Thr-61) lacking domain interaction did not induce mitochondrial dysfunction in N2A cells, indicating that the effect is specific to apoE4-expressing cells and dependent on domain interaction. Consistent with this finding, treatment of apoE4-expressing N2A cells with a small molecule that disrupts apoE4 domain interaction restored mitochondrial respiratory complex IV levels. These results suggest that pharmacological intervention with small molecules that disrupt apoE4 domain interaction is a potential therapeutic approach for apoE4-carrying AD subjects.
 ...
PMID:Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease. 2111 11