Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.5 (NADH dehydrogenase)
 2,135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike epidoses (MELAS) affecting mother, son and daughter is described. Biochemical studies on muscle biopsy specimen in one patient revealed NADH dehydrogenase (complex I) deficiency. A mitochondrial angiopathy could be demonstrated by brain and muscle biopsy. It is suggested that the mitochondrial angiopathy is the basic pathogenic mechanism of impaired cerebral circulation in MELAS.
 ...
PMID:Mitochondrial angiopathy in a family with MELAS. 132 8

A mitochondrial defect was investigated in an infant with fatal congenital lactic acidosis (3-14 mM), high lactate-to-pyruvate ratio, hypotonia, and cardiomyopathy. His sister had died with a similar disorder. Resting oxygen consumption was 150% of controls. Pathological findings included increased numbers of skeletal muscle mitochondria (many with proliferated, concentric cristae), cardiomegaly, fatty infiltration of the viscera, and spongy encephalopathy. Mitochondria from liver and muscle biopsies oxidized NADH-linked substrates at rates 20-50% of controls, whereas succinate oxidation by muscle mitochondria was increased. Mitochondrial NADH dehydrogenase activity (complex I, assayed as rotenone-sensitive NADH oxidase, NADH-duroquinone reductase, and NADH-cytochrome c reductase) was 0-10% of controls, and NADH-ferricyanide reductase activity was 25-50% of controls in the mitochondria and in skin fibroblasts. Activities of other electron transport complexes and related enzymes were normal. Familial deficiency of a component of mitochondrial NADH dehydrogenase (complex I) proximal to the rotenone-sensitive site thus accounts for this disorder.
 ...
PMID:Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy. 311 Feb 16

Thirteen of 15 patients with complex I deficiency had the multisystemic form, with strokelike episodes and other symptoms that fulfilled the diagnostic requirements for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), and 2 had only muscle fatigability and weakness, having the purely myopathic form. In the multisystemic form, 12 patients had ragged-red fibers. All multisystemic patients had myopathic histochemical abnormalities that consisted of mild to moderate variation in fiber size, disorganized intermyofibrillar networks, type 2 fiber atrophy, and an increased number of type 2C fibers. Five of 13 multisystemic patients had decreased cytochrome c oxidase (CCO) activity in extrafusal fibers, with sparing of intrafusal muscle fibers. In the myopathic form, pathological findings were similar to those in the multisystemic form. In addition to complex I and NADH dehydrogenase activities being decreased, the CCO activity was significantly decreased (less than 50% of control value) in 8 patients, especially when the disease was in its advanced stages, suggesting that CCO enzyme might be secondarily affected as the disease progresses.
 ...
PMID:Findings in muscle in complex I (NADH coenzyme Q reductase) deficiency. 314 39

Diabetic encephalopathy, characterized by cognitive deficits involves hyperglycemia-induced oxidative stress. Impaired mitochondrial functions might play an important role in accelerated oxidative damage observed in diabetic brain. The aim of the present study was to examine the role of mitochondrial oxidative stress and dysfunctions in the development of diabetic encephalopathy along with the neuroprotective potential of N-acetylcysteine (NAC). Chronic hyperglycemia accentuated mitochondrial oxidative stress in terms of increased ROS production and lipid peroxidation. Significant decrease in Mn-SOD activity along with protein and non-protein thiols was observed in the mitochondria from diabetic brain. The activities of mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase and cytochrome oxidase were decreased in the diabetic brain. Increased mitochondrial oxidative stress and dysfunctions were associated with increased cytochrome c and active caspase-3 levels in cytosol. Electron microscopy revealed mitochondrial swelling and chromatin condensation in neurons of diabetic animals. NAC administration, on the other hand was found to significantly improve diabetes-induced biochemical and morphological changes, bringing them closer to the controls. The results from the study provide evidence for the role of mitochondrial oxidative stress and dysfunctions in the development of diabetic encephalopathy and point towards the clinical potential of NAC as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and/or delaying the progression of CNS complications.
 ...
PMID:Protective effect of N-acetylcysteine supplementation on mitochondrial oxidative stress and mitochondrial enzymes in cerebral cortex of streptozotocin-treated diabetic rats. 2105 8

The natural carotenoid lycopene (LYC) has strong antioxidant and neuroprotective capacities. This study investigated the effects and mechanisms of LYC on chronic stress-induced hippocampal lesions and learning and memory dysfunction. Rats were administered LYC and/or chronic restraint stress (CRS) for 21 days. Morris water maze results demonstrated that LYC prevented CRS-induced learning and memory dysfunction. Histopathological staining and transmission electron microscopy observation revealed that LYC ameliorated CRS-induced hippocampal microstructural and ultrastructural damage. Furthermore, LYC alleviated CRS-induced oxidative stress by reducing reactive oxygen species (ROS) production and enhancing antioxidant enzyme activities. LYC also improved CRS-induced hippocampal mitochondrial dysfunction by recovering mitochondrial membrane potential, and complex I (NADH dehydrogenase) and II (succinate dehydrogenase) activities. Moreover, LYC reduced CRS-induced apoptosis via the mitochondrial apoptotic pathway, and decreased the number of terminal deoxynucleotidyl transferase dUTP nick-end-labeled positive cells. Additionally, western blot analysis demonstrated that LYC inhibited CRS-induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway. Correlation analysis indicated that ROS levels, JNK activation, and the mitochondrial apoptotic pathway were positively correlated. Further investigation of the underlying mechanisms revealed that the ROS scavenger N-acetyl-l-cysteine inhibited CRS-induced JNK activation. Furthermore, the JNK inhibitor SP600125 relieved CRS-induced hippocampal mitochondrial dysfunction, apoptosis via the mitochondrial apoptotic pathway, and learning and memory dysfunction. Together, these results suggest that LYC alleviates hippocampal oxidative stress, mitochondrial dysfunction, and apoptosis by inhibiting the ROS/JNK signaling pathway, thereby improving CRS-induced hippocampal injury and learning and memory dysfunction. This study provides a theoretical basis and new therapeutic strategies for the application of LYC to relieve chronic stress encephalopathy.
 ...
PMID:Lycopene ameliorates chronic stress-induced hippocampal injury and subsequent learning and memory dysfunction through inhibiting ROS/JNK signaling pathway in rats. 3281 May 85