INOSITOL 1,4,5-trisphosphate (InsP3) mediates the effects of several neurotransmitters, hormones and growth factors by mobilizing Ca2+ from a vesicular, non-mitochondrial intracellular store1 Many studies have indirectly suggested the endoplasmic reticulum (ER) to be the site of InsP3 action2–6, though some have implicated the plasma membrane7,8 or a newly described smooth surfaced structure, termed the calciosome9 Using antibodies directed against a purified InsP3-receptor glycoprotein10, of relative molecular mass 260,000, in electron microscope immunocytochemical studies of rat cerebellar Purkinje cells, we have now localized the InsP3 receptor to ER, including portions of the rough endoplasmic reticulum, a population of smooth-membrane-bound organelles (smooth ER), a portion of subplas-malemmal cisternae and the nuclear membrane, but not to mitochondria or the cell membrane These results suggest that in cerebellar Purkinje cells, InsP3-induced intracellular calcium release is not the property of a single organelle, but is effected by specialized portions of both rough and smooth ER, and possibly by other smooth surfaced structures The present findings are the first immunocytochemical demonstration of an InsP3 receptor within a cell

Inositol 1,4,5-trisphosphate receptor localized to endoplasmic reticulum in cerebellar Purkinje neurons.

The history of the cholinergic hypothesis

Interaction of protein domains in the assembly and mechanism of 2-oxo acid dehydrogenase multienzyme complexes.- Probing the active site of mammalian pyruvate dehydrogenase.- Role of the E2 core in the dominant mechanisms of regulatory control of mammalian pyruvate dehydrogenase complex.- Lipoamide dehydrogenase.- Plant pyruvate dehydrogenase complexes.- Regulation of the pyruvate dehydrogenase complex during the aerobic/anaerobic transition in the development of the parasitic nematode, Ascaris suum.- Structure, function and assembly of mammalian branched-chain ?-ketoacid dehydrogenase complex.- Lipoylation of E2 component.- Pyruvate dehydrogenase phosphatase.- The mitochondrial ?-ketoacid dehydrogenase kinases: Molecular cloning, tissue-specific expression and primary structure analysis.- Shorter term and longer term regulation of pyruvate dehydrogenase kinases.- Hormonal and nutritional modulation of PDHC activity status.- Regulation of branched-chain ?-keto acid dehydrogenase complex in rat liver and skeletal muscle by exercise and nutrition.- Dephosphorylation of PDH by phosphoprotein phosphatases and its allosteric regulation by inositol glycans.- Long-term regulation and promoter analysis of mammalian pyruvate dehydrogenase complex.- The sperm-specific pyruvate dehydrogenase E1? genes.- Molecular defects of the branched-chain ?-keto acid dehydrogenase complex: maple syrup urine disease due to mutations of the E1? or E1? subunit gene.- Human defects of the pyruvate dehydrogenase complex.- Multigenic basis for maple syrup urine disease with emphasis on mutations in branched chain dihydrolipoyl acyltransferase.- Structure and chromosomal localization of the human 2-oxoglutarate dehydrogenase gene.- Pyruvate dehydrogenase complex as an autoantigen in primary biliary cirrhosis.

Alpha-Keto Acid Dehydrogenase Complexes

• Since previous studies have suggested that the coupling of oxidation to phosphorylation is impaired in Alzheimer brain and fibroblasts, the effects of carbonyl cyanidem-chlorophenylhydrazone, a hydrazone known to uncouple mitochondrial oxidative phosphorylation, were tested on the development of immunoreactivity with antibodies to "Alzheimer antigens" in cultured fibroblasts from cognitively intact subjects. The fibroblasts were exposed for 10 to 14 days to a medium (DMd) modeled on media that favor neuronal differentiation in fetal brain cultures. The addition of a 10-μm concentration of carbonyl cyanidem-chlorophenylhydrazone to the DMd culture medium increased by more than 10-fold the proportion of cells reacting immunocytochemically with antibodies to paired helical filaments and by 157-fold the proportion of cells reacting with the Alz-50 monoclonal antibody. These observations suggest that the oxidative abnormalities previously described in tissues from patients with Alzheimer's disease may contribute to the accumulation of abnormal cytoskeletal materials in this disorder.

Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation.

Damage from oxidative stress and mitochondrial dysfunction occur together in many common neurodegenerative diseases. The enzymes that form the mitochondrial α-ketoglutarate-dehydrogenase complex (KGDHC), a key and arguably rate-limiting enzyme system of the tricarboxylic acid cycle, might mediate the interaction of these processes. KGDHC activity is reduced in numerous age-related neurodegenerative diseases and is diminished by oxidative stress. In Alzheimer’s disease (AD), the reduction correlates highly to diminished mental performance. Thus, research has focused on the mechanisms by which select oxidants reduce KGDHC and the consequences of such a reduction. Diminished KGDHC in cells is associated with apoptosis without changes in the mitochondrial membrane potential. Studies of isolated mitochondria and of animal models suggest that a reduction in KGDHC can predispose to damage by other toxins that promote neurodegeneration. Diminished oxidative metabolism can be plausibly linked to pathological features of neurodegenerative diseases (e.g., reduced mental function, the plaques and tangles in AD). Thus, reductions in KGDHC might be central to the pathophysiology of these diseases. Studies of proteins, cells, animal models, and humans suggest that treatments to diminish, or bypass, the reduction in KGDHC might be beneficial in age-related neurodegenerative disorders.

The α‐Ketoglutarate Dehydrogenase Complex

Pyruvate dehydrogenase complex (PDHC; EC 1.2.4.1, EC 2.3.1.12 and EC 1.6.4.3) includes 3 catalytically active mitochondrial enzymes involved in the formation of cellular energy through the tricarboxylic acid cycle and in the synthesis of ACh. We sought to determine whether immunocytochemically detected PDHC was enriched in neurons of the rat CNS, and, if so, whether the perikarya containing higher levels of PDHC immunoreactivity were differentially distributed with respect to their size or location within nuclear groups containing ACh, catecholamines or other unidentified transmitters. Under the labeling conditions used in this study, the peroxidase-antiperoxidase immunoreaction product for PDHC was detectable principally in neuronal perikarya. The intensity of immunoreactivity within perikarya was variable as judged visually and by cellular, computer-assisted densitometry. In the forebrain, the most intensely labeled perikarya were seen in the medial septal nuclei, the nuclei of the diagonal band, the nuclei basalis, the dorsal and ventral striatum, and the entorhinal cortex. More caudally, intense immunoreactivity was detected in perikarya in the supraoptic hypothalamic nuclei, reticular thalamic nuclei, lateral substantia nigra, most of the tegmental nuclei, lateral nuclei of the trapezoid body, raphe pontis and obscuris, and the caudal part of the lateral reticular nuclei. In addition, many of the motor nuclei of the cranial nerves, including the dorsal motor nuclei of the vagus and the hypoglossal nuclei, and the nucleus ambiguus contained perikarya with intense PDHC labeling. Densitometry revealed no differences in intensity of immunoreactivity in soma of varying sizes. However, the intensity of neuronal labeling for PDHC was significantly greater in several nuclear groups that were shown in adjacent sections to contain cholinergic, but not catecholaminergic, enzymes. In contrast, the primary olfactory cortex, pyramidal cell layer of the regio inferior of hippocampus, and the Purkinje cell layer of the cerebellum were regions having perikarya with intense PDHC immunoreactivity but lacking both the synthetic and the degradative enzymes for ACh. These results provide the first morphological evidence that PDHC, a general metabolic enzyme complex, is enriched in selective perikarya that are heterogeneously distributed in brain and are especially abundant in many of the regions containing cholinergic neurons. The heterogeneity of PDHC immunoreactivity suggests that certain cholinergic as well as noncholinergic nuclei may be selectively vulnerable to mitochondrial diseases involving pyruvate utilization.

https://www.jneurosci.org/content/jneuro/7/10/3171.full.pdf

Light microscopic immunocytochemical localization of pyruvate dehydrogenase complex in rat brain: topographical distribution and relation to cholinergic and catecholaminergic nuclei

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

KF Sheu

Author Tools

Chat about Author

Papers

Light microscopic immunocytochemical localization of pyruvate dehydrogenase complex in rat brain: topographical distribution and relation to cholinergic and catecholaminergic nuclei