Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monospecific antibodies to glutamate were used to characterize the organization of excitatory neurons and the plasticity of glutamate expression in the macaque striate cortex. Somata and processes immunoreactive for glutamate were densely and unevenly distributed in layers II-III, IVA, IVC. In tangential sections through layers II and III, patches of intense glutamate immunostaining were observed and were found to coincide with regions of the cytochrome oxidase (CO)-rich puffs. By contrast, clusters of intense immunostaining were surrounded by the lightly immunostained but intensely CO-stained lattice in layer IVA. Similarly, in layer IVC, focal aggregates of intense glutamate immunoreactivity were interspersed among regions of light immunostaining but intense CO staining. Glutamate immunoreactivity was also intense in layer VI but was much lighter in layers I, IVB, and V. Throughout the striate cortex, neurons resembling pyramidal cells and spiny stellate cells and processes that included dendrites and axons were immunostained. None of the glutamate-positive neurons was GABA immunoreactive. Following monocular deprivation of adult monkeys by intravitreal injections of TTX into one eye, glutamate immunoreactivity in layers IVC was distributed in alternating intensely and lightly stained stripes. The stripes of reduced immunostaining, which contained an abnormally low concentration of glutamate neurons and pale neuropil, corresponded to columns dominated by the TTX-injected eye. Similar stripes of alternating intense and light immunoreactivity were seen in layers II-III, where they corresponded to rows of puffs at the centers of intact-eye and deprived-eye columns, respectively. These findings demonstrate that glutamate-immunoreactive neurons and terminals in monkey striate cortex are densely concentrated in layers receiving direct geniculocortical innervation. In addition, the glutamate neurons and terminals form discrete units, which in layers II and III coincide precisely with regions receiving geniculocortical terminations but in layers IVA are segregated from these terminations. The findings also indicate that glutamate immunoreactivity is regulated by visually driven activity, and suggest that monocular deprivation in adulthood leads to a reduction in the major excitatory neurotransmitter in visual cortex as well as previously indicated reductions in GABA, the major inhibitory neurotransmitter.
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PMID:Neuronal characterization, compartmental distribution, and activity-dependent regulation of glutamate immunoreactivity in adult monkey striate cortex. 750 64

Protein phosphorylation and dephosphorylation play an important role in neuronal signal transduction. In this study the distribution of calcineurin, a calcium/calmodulin-dependent protein phosphatase, was investigated in the striate cortex of two Old World monkeys, Macaca fascicularis and Papio anubis, using a well-characterized, affinity-purified polyclonal antibody to calcineurin. In order to relate the calcineurin distributions to established cytochemical markers, adjacent sections were processed for the visualization of cytochrome oxidase. The staining patterns obtained from the two species were remarkably similar. The results indicate that (1) monkey striate cortex exhibits strong calcineurin-like immunoreactivity that is present both in the neuropil and in neurons, most of which have characteristics of pyramidal cells; (2) the distribution of calcineurin is laminar specific; and (3) it is complementary to that of cytochrome oxidase activity with respect to both its laminar and its tangential pattern. In sections perpendicular to the cortical lamination calcineurin immunoreactivity is high in layers II and III, reduced in layer IVA, nearly as dense as in supragranular layers in layer IVB, minimal in layer IVC, and again enhanced, but not as much as in supragranular layers, in layers V and VI. In addition to these lamina-specific variations, the density of calcineurin-like immunoreactivity exhibits a periodic modulation along trajectories parallel to the pial surface that is most marked in layer III but also discernable in infragranular layers. Accordingly, in tangential sections through supragranular layers the calcineurin distribution is mosaic-like with patches of high density corresponding to cytochrome-poor regions (interblob regions) and zones of low density corresponding to areas of high cytochrome oxidase activity (blobs).
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PMID:Laminar and columnar organization of immunoreactivity for calcineurin, a calcium- and calmodulin-regulated protein phosphatase, in monkey striate cortex. 770 89

Subunit proteins that make up functional GABAA receptors were localized immunocytochemistry in the primary visual cortex (area 17) of adult monkeys and humans. Immunoreactivity for the alpha 1, beta 2/3, and gamma 2 subunits is greatest in layers (II-III, IVA and IVC) of monkey area 17 that contain the highest density of GABA neurons and terminals. Immunostaining for each subunit is unevenly distributed in layers II and III, where patches of immunoreactivity correspond to regions of intense cytochrome oxidase (CO) staining, and in layer IVA, where intense immunoreactivity forms a honeycomb pattern identical to the CO staining pattern. Immunoreactivity for the subunits is localized principally within the neuropil, which, by simultaneous comparison with the distribution of microtubule-associated protein immunostaining, was found to include bundles of thin dendrites and zones of numerous dendritic segments. In addition, gamma 2 immunostaining surrounds the somata of a subpopulation of GABAergic neurons, immunoreactive for the calcium-binding protein parvalbumin. All three subunits are present in the somata and processes of neurons that occupy the white matter subjacent to monkey area 17. In human visual cortex, the alpha 1, beta 2/3, and gamma 2 subunits are distributed in a manner similar to that found in monkeys, with relatively intense immunostaining in layers IVC and IVA. In layer IVC, vertical stripes of intense receptor immunostaining (20-30 microns wide) alternate with wider stripes of pale immunostaining (30-60 microns wide). In the upper and lower halves of IVC beta, these stripes form lattices similar to those in layers IVC and IVA of monkeys. Following monocular deprivation by intravitreal injections of TTX in adult monkeys, immunoreactivity for each subunit in layer IVC consists of alternating intensely and lightly stained stripes. Comparison with the pattern of CO staining indicates that intense immunostaining for alpha 1, beta 2/3, and gamma 2 occurs in normal-eye stripes while abnormally light immunostaining is present in deprived-eye stripes. For all three subunits, immunoreactivity in deprived-eye stripes is reduced within 5 d of monocular deprivation and remains abnormally low for deprivations that extend to at least 30 d. These findings indicate that each of several GABAA receptor subunits adopt similar laminar and compartmental distributions in monkey and human area 17 and are likely to be expressed by the same neurons. The deprivation-dependent reduction in immunoreactivity for alpha 1, beta 2/3, and gamma 2 subunits suggests that all are regulated by visually driven activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GABAA receptor subunit immunoreactivity in primate visual cortex: distribution in macaques and humans and regulation by visual input in adulthood. 815 75

Subunit proteins that comprise functional AMPA receptors were localized by immunocytochemical methods in the adult macaque primary visual cortex (V1). GluR1, GluR2/3/4c, and GluR4 immunoreactivity consisted of rich plexuses of punctate profiles scattered throughout the neuropil, in radial arrays, and outlining the membrane of somata and proximal dendrites. Cytoplasmic immunoreactivity was limited. GluR2/3/4c immunostaining was more prominent along the somata surface and exhibited greater levels of cytoplasmic immunoreactivity than GluR1 and GluR4 immunostaining. The density of AMPA subunit immunoreactive elements also varied across layers and compartments of macaque V1. Immunoreactivity for GluR1, GluR2/3/4c, and GluR4 was densest in three bands that corresponded to layers IVA, IVC, and VI. Immunostaining for each subunit was also unevenly distributed within many of the layers. In layers II-III, patches of intense immunostaining coincided with cytochrome oxidase (CO)-rich blobs. In layer IVA, intense subunit staining formed a conspicuous honeycomb pattern. In layer IVC, subunit staining formed a radial lattice. GluR2/3/4c subunit immunostaining was also preferentially distributed within the CO-rich blobs of layers V-VI. These findings demonstrate that AMPA subunit immunoreactivity is densely concentrated in layers and compartments receiving direct geniculocortical innervation. This distribution, which differs from that of excitatory synapses, suggests that the density of AMPA receptors is unevenly distributed at synaptic and possibly extrasynaptic sites within macaque visual circuits.
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PMID:Immunocytochemical characterization of AMPA-selective glutamate receptor subunits: laminar and compartmental distribution in macaque striate cortex. 909 68

The possibility of a modular organization of non-neuronal elements was analyzed in the opercular region of the striate neocortex in adult New World monkeys. For this purpose, and in order to follow possible correlations in the general organization of neuronal and astroglial elements, immunocytochemical procedures for Glial Fibrillary Acid Protein (GFAP) and Microtubule Associated Protein 2 (MAP-2), in addition to cytochrome oxidase (COX) histochemistry, were applied to tangential and coronal sections and analyzed by using computer-assisted procedures. Astroglial interlaminar processes stemming from superficial laminae did not traverse lamina IVA, and thus did not appear in deeper layers. Clearly definable interlaminar processes were predominantly concentrated in laminae II-III. A honeycomb- like lattice was observed in tangential sections, with a "cell" size distribution similar to the MAP-2-IR lattice, suggesting an intimate association with the pyramidal columns. Additionally, analysis of similar sections disclosed the periodic appearance of large patches with high density of interlaminar processes, indicating a nonhomogeneous distribution of GFAP-IR processes in the striate cortex. COX "blobs" appeared frequently to coincide with areas expressing high density of GFAP-IR elements. These findings add a new perspective to current concepts of astroglial organization in the striate cortex of primates and reveal the existence of a non-neuronal modular organization in the primate striate cerebral cortex, and suggest that possible correlations between relative distributions of neuronal and astroglial elements should be further analyzed in cortical areas with a clear modular organization such as the striate cortex.
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PMID:Patterned distribution of immunoreactive astroglial processes in the striate (V1) cortex of New World monkeys. 988

Previous studies have shown that a transcription factor of the Ets family, nuclear respiratory factor 2 (NRF-2), can activate in vitro the gene expression of cytochrome oxidase (CO), a mitochondrial enzyme of oxidative metabolism. The goals of our present study were to determine whether the distribution of NRF-2 alpha subunit proteins correlated with that of CO activity in the macaque monkey visual cortex and whether the level could be perturbed by visual deprivation. We generated polyclonal antibodies specifically against human NRF-2 alpha subunit. In normal monkeys, patterns of NRF-2 alpha distribution resembled closely that of CO activity: 1) NRF-2 alpha immunoreactivity was localized in both nuclei and cytoplasm of neurons, but the levels differed among various laminae; 2) layers IVA, IVC, and VI, which had high CO activity, were labeled more densely by NRF-2 alpha than layers I, IVB, and V, which contained lower levels of both NRF-2 alpha and CO activity; and 3) CO-rich puffs in layers II and III contained a higher level of NRF-2 alpha than CO-poor interpuffs. From 1 day to 7 days after monocular impulse blockade with tetrodotoxin, there was a progressive reduction of NRF-2 alpha in deprived ocular dominance columns, in parallel with decreases in CO activity. These results suggest that local levels of NRF-2 in the monkey visual cortex closely reflect neuronal physiological and metabolic levels revealed by CO activity and that the expression of NRF-2 alpha, like that of CO, is regulated tightly by neural functional activity.
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PMID:Nuclear respiratory factor-2 subunit protein: correlation with cytochrome oxydase and regulation by functional activity in the monkey primary visual cortex. 995 50

Glutamate and its various receptors are known to play an important role in excitatory synaptic transmission throughout the CNS, including the primary visual cortex. Among subunits of the AMPA receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid), subunit 2 (GluR2) is of special significance because it controls their Ca2+ permeability. In the past, this subunit has been studied mostly in conjunction with other AMPA subunits. The present study sought to determine if GluR2 alone has a distinct laminar distribution in the normal macaque visual cortex, and if its pattern correlated with that of cytochrome oxidase (CO) under normal and monocularly deprived conditions. In the normal adult cortex, GluR2 immunoreactivity (ir) had a patchy distribution in layers II/III, in register with CO-rich puffs. GluR2-ir highlighted the upper border of layer II, the lower border of layer IV (previously termed IVC(beta dark)) and, most prominently, layer VI. Labeled neurons were primarily of the pyramidal type present in the upper border and lower half of layer VI, layers II/III, and scattered in layers V and upper IVB. Labeled nonpyramidal cells were large in layer IVB and small in IVC(beta dark). Notably, the bulk of CO-rich layers IVC and IVA had very low levels of GluR2-ir. At fetal day 13, however, GluR2 labeling showed a honeycomb-like pattern in layer IVA not found in the adult. A fragment of GluR2 cDNA was generated from a human cDNA library, and in situ hybridization revealed an expression pattern similar to that of GluR2 proteins. After 1-4 weeks of monocular impulse blockade with tetrodotoxin (TTX), alternating rows of strong and weak GluR2-ir in layers VI and II/III appeared in register with CO-labeled dark and light ocular dominance columns in layer IVC and puffs in II/III, respectively. Our results indicate that various cortical layers are differentially influenced by glutamate. The bulk of the major geniculate-recipient layers IVC and IVA have low levels of GluR2, presumably favoring synaptic transmission via Ca(2+)-permeable glutamate receptors. GluR2 plays a more important role in supragranular and infragranular layers, where the initial geniculate signals are further modified and are transmitted to other cortical and subcortical centers. The maintenance of GluR2 in these output layers is governed by visual input and neuronal activity, as monocular impulse blockade induced a down-regulation of this subunit in deprived ocular dominance columns.
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PMID:AMPA glutamate receptor subunit 2 in normal and visually deprived macaque visual cortex. 1250 23

Human head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide, possibly due to the significant role of alcohol and tobacco use in its development. Underlying most cancers are defects in mitochondrial functions such as energy metabolism and apoptosis. In fact, the mutations in mitochondrial DNA (mtDNA), which encode proteins for oxidative phosphorylation (OXPHOS), have been associated with human head and neck cancers. Here, we investigated the changes in the expression of OXPHOS complexes and the contribution of the defects in mitochondrial translation in the progression of HNSCC. Western blot analyses of the several stage IVA HNSCC primary tumors have shown reduction in the expression of COII and ATP5A of the OXPHOS complexes IV and V subunits, respectively. On the other hand, expression of the majority of the OXPHOS subunits, except complex II SDHB subunit, was impaired in a patient with a stage IV tumor with a regional lymph node. Interestingly, an overall reduction in one of the mitochondrial-encoded subunits of the complex IV, COII, accentuated a possible defect in mitochondrial translation machinery in two of the stage IVA tumors. Evidence provided in this study suggests for the first time that the mitochondrial translation defect(s) could be due to a decrease in the expression of one of the essential mitochondrial ribosomal proteins, MRPL11, in head and neck tumor biopsies. We also observed an acquired mitochondrial translation deficiency in the HN8 cell line derived from a lymph node metastasis but not in the HN22 cells derived from the primary tumor of the same patient. These seminal observations suggest that the mitochondrial translation machinery deserves further investigation for accurate molecular assessment and treatment of HNSCC.
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PMID:Impaired mitochondrial protein synthesis in head and neck squamous cell carcinoma. 2623 94


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