Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selegiline inhibits the activity of monoamine oxidase B, enhances the release of dopamine, blocks the uptake of dopamine, acts as a calmodulin antagonist, and enhances the level of cyclic AMP, which in turn protects dopaminergic neurons. It possesses cognition-enhancing functions, rejuvenates serum insulin-like growth factor I in aged rats, and enhances life expectancy in rodents. Selegiline possesses neurotrophic-like actions, and rescues axotomized motorneurons independent of monoamine oxidase B inhibition. It enhances the synthesis of nerve growth factor, protects dopaminergic neurons from glutamate-mediated neurotoxicity, and protects dopaminergic neurons from toxic factors present in the spinal fluid of parkinsonian patients, and the said effect may be mediated via elaborating brain derived neurotrophic factor. Selegiline increases the striatal superoxide dismutase, protects against peroxynitrite- and nitric oxide-induced apoptosis, and guards dopaminergic neurons from toxicity induced by glutathione depletion. It stimulates the biosynthesis of interleukin 1-beta and interleukin-6, is an immunoenhancing substance, possesses antiapoptotic actions, and is neuroprotectant in nature. Selegiline has been shown to be efficacious in Parkinson's disease, global ischemia, Gille de la Tourette syndrome, and narcolepsy. Its therapeutic efficacy in Alzheimer's disease remains uncertain. In Alzheimer's disease, short term studies of selegiline suggest a beneficial effect; whereas long term studies are less convincing.
 ...
PMID:Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases. 1710 May 91

We investigated the effect of N-acetyl-l-cysteine (NAC) on the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, antioxidant enzymes, and inflammatory markers in diabetic rat hearts. Metabolic parameters, free 15-F(2t)-isoprostane level, protein expression of NADPH oxidase, superoxide dismutase (SOD), heme oxygenase (HO-1), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) were analyzed in control and streptozotocin-induced diabetic rats treated with or without NAC in drinking water for 8 wk. The cardiac protein expression of p67(phox) and p22(phox) was increased in diabetic rats, accompanied by increased NADPH-dependent superoxide production. As a compensatory response to the increased NADPH oxidase, the protein expression of Cu-Zn-SOD and HO-1 and the total SOD activity were also increased in diabetic rat hearts. Consequently, cardiac free 15-F(2t)-isoprostane, an index of oxidative stress, was increased in diabetic rats, indicating that the production of reactive oxygen species becomes excessive in diabetic rat hearts. Cardiac inflammatory markers IL-6 and COX-2 were also increased in diabetic rats. NAC treatment prevented the increased expression of p22(phox) and translocation of p67(phox) to the membrane in diabetic rat hearts. Subsequently, the levels of cardiac free 15-F(2t)-isoprostane, HO-1, Cu-Zn-SOD, total SOD, IL-6, and COX-2 in diabetic rats were decreased by NAC. Consequently, cardiac hypertrophy was attenuated in diabetic rats treated with NAC. The protective effects of NAC on diabetic rat hearts may be attributable to its protection of hearts against oxidative damage induced by the increased NADPH oxidase and to its reduction in cardiac inflammatory mediators IL-6 and COX-2.
 ...
PMID:Downregulation of NADPH oxidase, antioxidant enzymes, and inflammatory markers in the heart of streptozotocin-induced diabetic rats by N-acetyl-L-cysteine. 1712 89

Thiazolidinediones (TZDs) are synthetic agonists of the ligand-activated transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma). TZDs are known to curtail inflammation associated with peripheral organ ischemia. As inflammation precipitates the neuronal death after stroke, we tested the efficacy of TZDs in preventing brain damage following transient middle cerebral artery occlusion (MCAO) in adult rodents. As hypertension and diabetes complicate the stroke outcome, we also evaluated the efficacy of TZDs in hypertensive rats and type-2 diabetic mice subjected to transient MCAO. Pre-treatment as well as post-treatment with TZDs rosiglitazone and pioglitazone significantly decreased the infarct volume and neurological deficits in normotensive, normoglycemic, hypertensive and hyperglycemic rodents. Rosiglitazone neuroprotection was not enhanced by retinoic acid x receptor agonist 9-cis-retinoic acid, but was prevented by PPARgamma antagonist GW9662. Rosiglitazone significantly decreased the post-ischemic intercellular adhesion molecule-1 expression and extravasation of macrophages and neutrophils into brain. Rosiglitazone treatment curtailed the post-ischemic expression of the pro-inflammatory genes interleukin-1beta, interleukin-6, macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, cyclooxygenase-2, inducible nitric oxide synthase, early growth response-1, CCAAT/enhancer binding protein-beta and nuclear factor-kappa B, and increased the expression of the anti-oxidant enzymes catalase and copper/zinc-superoxide dismutase. Rosiglitazone also increased the expression of the anti-inflammatory gene suppressor of cytokine signaling-3 and prevented the phosphorylation of the transcription factor signal transducer and activator of transcription-3 after focal ischemia. Thus, PPARgamma activation with TZDs might be a potent therapeutic option for preventing inflammation and neuronal damage after stroke with promise in diabetic and hypertensive subjects.
 ...
PMID:Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents. 1739 60

The proinflammatory cytokine interleukin-1beta (IL-1beta) contributes to inflammation and neuronal death in CNS injuries and neurodegenerative pathologies, and astrocytes have been implicated as the primary mediators of IL-1beta induced neuronal death. As astrocytes play an important role in supporting the survival and functions of neurons, we investigated the effect of plant flavonoids quercetin and luteolin, with known anti-inflammatory properties in modulating the response of human astrocytes to IL-1beta for therapeutic intervention. Flavonoids significantly decreased the release of reactive oxygen species (ROS) from astrocytes stimulated with IL-1beta. This decrease was accompanied by an increase in expression of superoxide dismutase (SOD-1) and thioredoxin (TRX1)-mediators associated with protection against oxidative stress. Flavonoids not only modulated the expression of astrocytes specific molecules such as glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and ceruloplasmin (CP) both in the presence and absence of IL-1beta but also decreased the elevated levels of proinflammatory cytokine interleukin-6 (IL-6) and chemokines interleukin-8 (IL-8), interferon-inducible protein (IP-10), monocyte-chemoattractant protein-1 (MCP-1), and RANTES from IL-1beta activated astrocytes. Significant decrease in neuronal apoptosis was observed in neurons cultured in conditioned medium obtained from astrocytes treated with a combination of IL-1beta and flavonoids as compared to that treated with IL-1beta alone. Our result suggests that by (i) enhancing the potential of activated astrocytes to detoxify free radical, (ii) reducing the expression of proinflammatory cytokines and chemokines, and (iii) modulating expression of mediators associated with enhanced physiological activity of astrocyte in response to injury, flavonoids confer (iv) protection against IL-1beta induced astrocyte mediated neuronal damage.
 ...
PMID:Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. 1749 37

Despite recent advances in understanding molecular mechanisms involved in glioblastoma progression, the prognosis of the most malignant brain tumor continues to be dismal. Because the flavonoid kaempferol is known to suppress growth of a number of human malignancies, we investigated the effect of kaempferol on human glioblastoma cells. Kaempferol induced apoptosis in glioma cells by elevating intracellular oxidative stress. Heightened oxidative stress was characterized by an increased generation of reactive oxygen species (ROS) accompanied by a decrease in oxidant-scavenging agents such as superoxide dismutase (SOD-1) and thioredoxin (TRX-1). Knockdown of SOD-1 and TRX-1 expression by small interfering RNA (siRNA) increased ROS generation and sensitivity of glioma cells to kaempferol-induced apoptosis. Signs of apoptosis included decreased expression of Bcl-2 and altered mitochondrial membrane potential with elevated active caspase-3 and cleaved poly(ADP-ribose) polymerase expression. Plasma membrane potential and membrane fluidity were altered in kaempferol-treated cells. Kaempferol suppressed the expression of proinflammatory cytokine interleukin-6 and chemokines interleukin-8, monocyte chemoattractant protein-1, and regulated on activation, normal T-cell expressed and secreted. Kaempferol inhibited glioma cell migration in a ROS-dependent manner. Importantly, kaempferol potentiated the toxic effect of chemotherapeutic agent doxorubicin by amplifying ROS toxicity and decreasing the efflux of doxorubicin. Because the toxic effect of both kaempferol and doxorubicin was amplified when used in combination, this study raises the possibility of combinatorial therapy whose basis constitutes enhancing redox perturbation as a strategy to kill glioma cells.
 ...
PMID:Kaempferol induces apoptosis in glioblastoma cells through oxidative stress. 1787 51

Sixty cases with primary knee OA were equally categorized into six groups with EHI (Gs 1, 2, 3) or without (Gs 4, 5, 6). GI included cases with HCV, GII cases with RHS & HCV and GIII cases with a history of non-active schistosomiasis whereas Gs 4, 5 & 6 included cases without EHI. Clinical examination with inclusion criteria of pathological manifestations w\as associated with biochemical evaluation of adhesion molecules (E-selectin, P-selectin, intracellular adhesion molecule-3 "ICAM-3") in plasma and synovial fluid. Synovial fluid indices (IgG, IgA, IgM, & C3) were evaluated as well as indices of inflammation and oxidative stress (Beta 2 microglobulin, Haptaglobulin, fibronectin, total thiol, superoxide dismutase, thiobarbituric acid reactive substance & hyaluronan) in synovial fluid and indices activating fibrogenesis in serum and plasma (procollagen III, plasma prolidase, Interleukin-1 beta, Interleukin-6 & TNF alpha). The results showed a positive relationship between indices activating vascular damage, fibrogenesis and immuno-inflammatory response with higher change magnitude in EHI cases particularly with combined HCV & RHS. This implement the dual role of hepatic insult and intestinal amoebiasis on immune mediated mechanisms activating inflammatory response in OA cases reflecting common signaling pathways associated with pathogenesis of multifaceted origin.
 ...
PMID:Dual impact of chronic liver disease and amaebiasis on immunopathogenesis of primary osteoarthritis in Egyptians. 1792 12

Acceleration of blood leukocyte apoptosis in major depression has been described. The present studies have been undertaken to estimate the level of apoptosis of blood leukocytes in patients with depression and to examine the mechanisms leading to apoptosis. Blood was taken from 29 patients with depression (age 48.2+/-11.2, 14 males, 15 females) and 30 healthy controls (age 41.3+/-4.1, 15 males, 15 females), and apoptosis was estimated by the cytometric method by measurements of annexin V binding, mitochondrial membrane potential (DeltaPsi), bcl-2, bax, and Fas (CD95) expression in CD4+, CD8+ and CD14+ cells. The amounts of cytochrome c released from mitochondria to cytosol of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were also measured. The levels of reactive oxygen species (ROS) released from PMNs were examined as was the serum activity of superoxide dismutase (SOD), catalase (CAT), and total peroxidase (PER). Additionally, serum levels of the tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) were estimated. Our experiments indicated accelerated apoptosis of CD4+ T lymphocytes and CD14+ cells (mainly neutrophils) of depressed patients as well as a significant increase in the percent of Fas-expressing cells. Bcl-2 and bax expression was higher in cells of depressed patients than in control, however, bcl-2/bax ratio was significantly decreased in CD14+ cells of depressed patients. PMNs isolated from the blood of the patients produced more ROS spontaneously and after induction with phorbol ester (PMA) than PMNs of the healthy control. A significant increase in serum activity of SOD, CAT and PER was also detected. Overproduction of superoxide anion correlated positively with the level of PMNs apoptosis (measured by cytochrome c release), suggesting that superoxide anion might be an important factor inducing apoptotic death of blood cells. The result of our experiment indicated that apoptosis of immune cells may affect patient's susceptibility to different infections and application of antioxidants in medication of patients with depression will be beneficial for them. The increased level of IL-6 in sera of the depressed patients did not correlate with overproduction of ROS, suggesting that this cytokine is not involved in oxidative stress and apoptosis of leukocytes.
 ...
PMID:Accelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression. 1808 80

Motorcycle exhaust (ME) from two-stroke engines contains many toxicants and poses a potential health hazard. The major objectives of the present study were to investigate the male reproductive toxicity of ME and the underlying mechanisms of toxicity. Male Wistar rats were exposed to ME by inhalation 1 h each in the morning and afternoon, Monday through Friday. Exposures to 1:50 diluted ME for 4 weeks or to 1:10 diluted ME for 2 and 4 weeks showed concentration- and time-dependent decreases of testicular weight, spermatid number, and cauda epididymal sperm number. Subsequent studies were done using 4-week exposure to 1:10 diluted ME. ME caused histopathological changes including testicular spermatocytic necrosis and seminiferous tubule atrophy and cauda epididymal formation of clusters of pyknotic and necrotic sperm cells. ME-exposed male rats mated with untreated females showed decreases of male mating index and female fertility index and an increase of implantation site loss. ME decreased 7-ethoxycoumarin O-deethylase and superoxide dismutase activities but induced proinflammatory cytokine interleukin-6 (IL-6) messenger RNA (mRNA) in the testis. Male rats were exposed to ME with or without cotreatment with 50 mg/kg vitamin E orally for 4 weeks. ME decreased serum testosterone concentration. This effect was reversed by cotreatment with vitamin E. ME decreased testicular spermatid number and induced IL-6 mRNA and protein. These effects were also reversed by the vitamin E cotreatment. The present findings show that ME causes male reproductive effects and induces testicular IL-6 in rats by mechanisms involving induction of oxidative stress and inhibition of steroidogenesis.
 ...
PMID:Motorcycle exhaust induces reproductive toxicity and testicular interleukin-6 in male rats. 1823 36

To investigate the effects of allicin supplementation on exercise-induced muscle damage (EIMD), interleukin-6 (IL-6), and antioxidative capacity, a double-blinded, placebo-controlled study was conducted in well-trained athletes. Subjects were randomly assigned to an allicin supplementation group (AS group) and a control group, and received either allicin or placebo for 14 days before and 2 days after a downhill treadmill run. Plasma creatine kinase (CK), muscle-specific creatine kinase (CK-MM), lactate dehydrogenase (LDH), IL-6, superoxide dismutase (SOD), total antioxidative capacity (TAC), and perceived muscle soreness were measured pre and post exercise. AS group had significantly lower plasma levels of CK, CK-MM and IL-6, and reduced perceived muscle soreness after exercise, when compared with the control group. AS group also demonstrated a trend toward reducing plasma concentration of LDH after exercise (P = 0.08), although not statistically significant. Allicin supplementation induced a higher value of TAC at rest, and this higher value was maintained 48 h after exercise, however, there was no difference in SOD values after exercise between the two groups. The results suggested that allicin might be a potential agent to reduce EIMD. Further studies concerning anti-inflammatory and anti-oxidative effects of allicin on EIMD are needed.
 ...
PMID:Effects of allicin supplementation on plasma markers of exercise-induced muscle damage, IL-6 and antioxidant capacity. 1830 54

Metallothionein (MT) as a potent antioxidant can affect energy metabolism. The present study was undertaken to investigate the association between MT gene polymorphism and type 2 diabetes mellitus. Using the PCR-based restriction fragment length polymorphism method, seven single nucleotide polymorphisms (SNPs) in MT genes (rs8052394 and rs11076161 in MT1A gene, rs8052334, rs964372, and rs7191779 in MT1B gene, rs708274 in MT1E gene, and rs10636 in MT2A gene) were detected in 851 Chinese people of Han descent (397 diabetes and 454 controls). Several serum measurements were also examined randomly for 43 diabetic patients and 41 controls. The frequency distributions of the G allele in SNP rs8052394 of MT1A gene were significantly associated with the incidence of type 2 diabetes. There was no difference between patients and controls for the rest of six SNPs. Serum levels of interleukin-6 and tumor necrosis factor-alpha were higher, and serum superoxide dismutase activity was significantly lower in the diabetic group than those in the control group. For diabetic patients, serum superoxide dismutase activity was significantly lower in GG or GA carriers than those of AA carriers of rs8052394 SNP. Increased serum levels in diabetic patients were positively associated with rs964372 SNP, and type 2 diabetes with neuropathy was positively associated with rs10636 and rs11076161. These results suggest that multiple SNPs in MT genes are associated with diabetes and its clinical symptoms. Furthermore, MT1A gene in rs8052394 SNP is most likely the predisposition gene locus for diabetes or changes of serum superoxide dismutase activity.
 ...
PMID:Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications. 1834 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>