Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the molecular basis of muscle atrophy, we have performed the serial analysis of gene expression (SAGE) method with control and immobilized muscles of 10 rats. The genes that expressed >0.5% in muscle are involved in the following three functions: 1) contraction (troponin I, C and T; myosin light chain 1-3; actin; tropomyosin; and parvalbumin), 2) energy metabolism (cytochrome c oxidase I and III, creatine kinase, glyceraldehyde-3-phosphate-dehydrogenase, phosphoglycerate mutase, ATPase 6, and aldolase A), and 3) housekeeping (lens epithelial protein). Muscle atrophy appears to be caused by changes in mRNA levels of specific regulators of proteolysis, protein synthesis, and contractile apparatus assembling, such as polyubiquitin, elongation factor 2, and nebulin. Immobilization has produced a decrease more than threefold in gene expression of enzymes involved in energy metabolism, especially ATPase, cytochrome c oxidase, NADH dehydrogenase, and protein phosphatase 1. Differential gene expressions of selenoprotein W and uroporphyrinogen decarboxylase, which can be involved in oxidative stress, were also observed. Other genes with various functions, such as cholesterol metabolism and growth factors, were also differentially expressed. Moreover, novel genes regulated by immobilization were discovered. Thus, the current study allows a better understanding of global muscle characteristics and the molecular mechanisms of sedentarity and sarcopenia.
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PMID:Characterization of control and immobilized skeletal muscle: an overview from genetic engineering. 1125 86

Ubiquitin proteasome system (UPS) and autophagy lysosome pathway (ALP) are the two most important routes for degradation of aggregated/misfolded proteins. Additionally, ALP is so far the only known route to clear entire organelles, such as mitochondria. We proposed that enhancement of ALP may be beneficial for some neurodegenerative disorders, such as Parkinson's disease (PD), in which the accumulation of aggregated/misfolded proteins and the dysfunction of mitochondria are the two major pathogenesis. Mitochondrial complex I inhibitor rotenone, which causes dysfunction mitochondria and UPS, has been considered as one of the neurotoxins related to PD. In this study, rotenone-exposed human neuronal SH-SY5Y cells were used as an in vitro model for us to determine whether autophagy enhancer rapamycin could protect against rotenone-induced injury and its underlying mechanisms. The observed results showed that rapamycin alleviated rotenone-induced apoptosis, whose effects were partially blocked when autophagy related gene 5 (Atg5) was suppressed by Atg5 small interference RNA (siRNA) transfection. Additionally, the results showed that rapamycin pretreatment diminished rotenone-induced accumulation of high molecular weight ubiquitinated bands, and reduced rotenone-induced increase of cytochrome c in cytosolic fraction and decreased mitochondrial marker cytochrome oxidase subunit IV (COX IV) in mitochondrial fraction. The changes in cytochrome c and COX IV indicated that the decreased translocation of cytochrome c from mitochondria to cytosol was probably due to the turn over of entire injured mitochondria. The results that lysosome and mitochondria were colocolized within the cells pretreated with rapamycin and that the mitochondria could be found within autophagy double membrane structures further supported that the damaged mitochondria might be cleared through autophagy, which process has been termed as "mitophagy." Our studies suggested that autophagy enhancer rapamycin is neuroprotective against rotenone-induced apoptosis through autophagy enhancement. We concluded that pharmacologically induction of autophagy by rapamycin may represent a useful therapeutic strategy as disease-modifiers in PD.
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PMID:Rapamycin protects against rotenone-induced apoptosis through autophagy induction. 1968 53

ABSTRUCT: Parkinson's disease (PD) is associated with progressive degeneration of melanin-containing dopamine neuron cell bodies arising in the substantia nigra pars compacta (SNpc) and projecting terminals to the striatum. The disease is best characterized biochemically as a deficiency of striatal dopamine. The mechanism of neurodegeneration remains an enigma despite a large body of investigation and several hypotheses (1-5). In the past decade much has been learned about the chemical pathology of the disease. This progress has been helped by elucidation of the mechanism of the neurotoxic actions of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which are used to induce animal models of this disease. Thus, the most valid current hypothesis concerning the pathogenesis of idiopathic PD is progressive oxidative stress (OS), which can generate excessive reactive oxygen species (ROS) selectively in the SNpc (1-9), and subsequent biochemical abnormalities (Table 1). In addition, the ROS scavenging system may also diminish, which would exaggerate the condition leading to accumulation of ROS. In PD, it is thought that both these events occur; Table 1 gives a summary of the biochemical changes identified to date in the SNpc of PD patients. Iron, monoamine oxidase B (MAO-B), copper/zinc superoxide dismutase (Cu/Zn-SOD), and heme oxygenase (radical producing) are increased; reduced glutathione (GSH) and vitamin C (radical scavenging) are decreased. Whether OS is a primary or secondary event in PD has not been established, but when it does occur, OS can lead to a cascade of events resulting in the demise of the nigrostriatal dopaminergic neurons. One approach toward protection of such neurons is the use of radical scavengers or iron chelators as neuroprotective drugs (10). Table 1 Biochemical Alterations in Substantia Nigra of Parkinson's Disease Indicating Oxidative Stress Elevated Decreased Iron (in microglia, astrocytes, oligodendrocytes, and melanized dopamine neurons and mitochondria) GSH (GSSG unchanged); GSH/GSSG ratio decreased Mitochondrial complex I Ferritin Calcium binding protein (calbindin 28) Mitochondrial monoamine oxidase B Transferrin and transferrin receptor Lipofuscin Vitamins E and C Ubiquitin Copper Cu/Zn-superoxide dismutase Cytotoxic cytokines (TNF-a, IL-1, IL-6) Inflammatory transcription factor NFKB Heme oxygenase-1 Ratio of oxidized to reduced glutathione (GSSG/GSH) Nitric oxide Neuromelanin.
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PMID:Oxidative stress indices in Parkinson's disease : biochemical determination. 2131 73