Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines exert autocrine and paracrine effects on the heart, some of which may be mediated by inducible nitric oxide synthase (i-NOS) expression. We studied the effects of cytokine-mediated NO synthesis on cell injury in the presence of deoxyglucose (DOG) and cyanide (CV)(20 mM DOG and 2 mM CN) for up to 3 hours and during recovery (18 hours). The influence of heat shock protein-70 on the extent of myocyte damage was also assessed. IL-1 beta and gamma-IFN act synergistically to enhance NO synthesis by cardiac myocytes. When these cytokines are present, the rate of ATP depletion after DOG and CN is significantly greater than in their absence. When IL-1 beta and gamma-IFN are added with the NOS inhibitor, L-monomethyl-L-arginine (L-NMMA), or when a cytokine that does not produce NO (TNF-alpha) is present, the rate of ATP depletion is no different from the rate seen with DOG and CN alone. After recovery for 18 hours, myocytes that were exposed to IL-1 beta and gamma-IFN release more lactic dehydrogenase and have significantly lower levels of ATP. L-NMMA decreases lactic dehydrogenase release and maintains ATP at levels similar to metabolically inhibited cells in the absence of these cytokines. Consistent with the decreased recovery in ATP with cells incubated with DOG and CN plus IL-1 beta and gamma-IFN is a decrease in cytochrome oxidase activity. Decreases in cellular ATP correspond to increased levels of heat shock protein-70 measured in myocytes after 18 hours of recovery after metabolic inhibition in the presence of IL-1 beta and gamma-IFN. In contrast, prior induction of heat shock protein-70 reduces the rate of ATP depletion in myocytes treated with DOG and CN and maintains ATP at levels that are significantly higher than those seen in non-heat-shocked cells. Recovery of cells exposed to heat shock is also greater, as seen by decreased lactic dehydrogenase and citrate synthase release. The heat-shocked myocytes contain significantly more glycogen than the cells that were not heat shocked. The increased cellular glycogen is likely responsible for the greater lactate production and slower rates of ATP depletion in the heat-shocked, metabolically inhibited cells. Cell survival under conditions of metabolic inhibition is closely related to cellular ATP preservation.
 ...
PMID:Response of the neonatal rat cardiomyocyte in culture to energy depletion: effects of cytokines, nitric oxide, and heat shock proteins. 897 76

This study was carried out to elucidate the pathophysiologic mechanism of cerebral hyperemia observed during the early phase of bacterial meningitis. We tested the hypothesis that microbial invasion through the blood-brain barrier is responsible for cerebral vasodilation and hyperemia in meningitis. Escherichia coli was given either intravenously (i.v.) or intracisternally (i.c.) to closely mimic the primary or secondary bacterial invasion occurring in meningitis and newborn piglets were grouped according to their invasion results (+ or -); 12 in the i.v. (+) group, 14 in the i.v. (-) group, 13 in the i.c. (+) group, 15 in the i.c. (-) group. The results were compared with eight animals in the control group. Near infrared spectroscopy (NIRS) was employed to monitor changes in total hemoglobin (HbT), oxygenated hemoglobin (HbO), deoxygenated hemoglobin (Hb), deduced hemoglobin (HbD), and oxidized cytochrome aa3 (Cyt aa3). HbT, as an index of cerebral blood volume, increased progressively in both i.v. (+) and i.v. (-) groups and became significantly different from control and baseline values at 2 h. Hb significantly increased only in i.v. (+) group. HbD, as an index of cerebral blood flow, decreased significantly in i.v. (+), i.v.(-) and i.c. (-) groups and this change was mitigated in i.c. (+) group, HbO was reduced in i.c. (-) group and this decrease was attenuated in i.c. (+) group. Increased Cyt aa3 was observed in all experimental groups after bacterial inoculation. Changes in ICP, blood pressure, cerebral perfusion pressure, blood or CSF glucose or lactate, CSF TNF-alpha level, or CSF leukocytes number were not associated with changes in NIRS findings. These findings suggest that primary or secondary bacterial invasion across the blood-brain barrier is primarily responsible for cerebral vasodilation and hyperemia observed during the early phase of bacterial meningitis.
 ...
PMID:Effects of microbial invasion on cerebral hemodynamics and oxygenation monitored by near infrared spectroscopy in experimental Escherichia coli meningitis in the newborn piglet. 1040 12

In osteoarthritis (OA) a time or age dependent process leads to aberrant cartilage structure which is characterized by reduced number of chondrocytes, loss of existing cartilage extracellular matrix, the production of matrix with abnormal composition and pathologic matrix calcification. Because chondrocyte matrix synthesis and mineralization are modulated by the balance between ATP generation and consumption, the mechanism by which chondrocytes generate energy have been a topic of interest. The analysis of mitochondrial respiratory chain (MRC) activity in OA chondrocytes shows a significant decrease in complexes II and III compared to normal chondrocytes. On the other hand, mitochondrial mass is increased in OA, as demonstrated by a significant rise in CS activity. Furthermore, OA cells show a reduction in the mitochondrial membrane potential (deltapsim) as demonstrated by using the fluorescent probe JC-1. OA cartilage contains high number of apoptotic chondrocytes, and mitochondria play a key role in apoptosis. Interestingly, OA cartilages show markedly elevated Bcl-2 and caspasa-3 expression. This expression is also correlated with chondrocyte apoptosis and OA lesions. The pathogenesis of OA includes elaboration of increased amounts of NO as a consequence of up-regulation of chondrocyte-inducible NO synthase induced by IL-1, TNF-alpha and other factors. NO reduces chondrocyte survival and induces cell death with morphologic changes characteristic of chondrocyte apoptosis. NO reduces the activity of complex IV and decreases the deltapsim as measured as the ratio of red/green fluorescence. Furthermore, NO induces the mRNA expression of caspase-3 and -7, and it reduces the expression of mRNA bcl-2 and the bcl-2 protein synthesis. Some studies suggest that the chondrocyte mitochondria are specialized for calcium transport and are important in the calcification of the extracellular matrix. Mineral formation has been demonstrated in matrix vesicles (MV) and within mitochondria. Direct suppression of mitochondrial respiration promoted MV-mediated mineralization in chondrocytes. Regulation of MRC may be one of the signaling pathways by which NO modulates articular cartilage matrix biosynthesis and pathologic mineralization. After age 40, the incidence of OA in humans increases progressively with increasing age. Studies show a trend to statistic significance between the age and the reduction of complex I activity of human normal chondrocytes. However, the study of relation between age and deltapsim in normal chondrocytes do not demonstrate any significant correlation. It has been reported that as the number of population doublings increased, mitochondrial DNA was degraded and the number of mitochondria per chondrocyte decline. One approach for determining the role of mitochondria in OA is to determine the effects of the MRC inhibition and to compare them with the findings in OA. Inhibition of MRC with antimycin prevents the normal ability of TGFbeta to increase excretion of Pi, thereby worsening deposition of pathologic HA crystals. In chondrocytes, the inhibition of complex IV with NaN3 modified both the deltapsim and the survival of cells inducing apoptosis. Inhibition of complex I with rotenone increases the expression and synthesis of Bcl-2 and Cox-2, both effects are similar effects to produced by IL-1 in human chondrocytes.
 ...
PMID:Mitochondrial dysfunction in osteoarthritis. 1612 Apr 27

Acute exercise in mice induces intestinal lymphocyte (IL) apoptosis. Freewheel running reduces apoptosis and forced exercise training increases splenocyte antioxidant levels. The purpose of this study was to examine the effect of freewheel running and acute exercise on mouse IL numbers and concentrations of apoptosis and antioxidant proteins and pro-inflammatory cytokines in IL. Female C57BL/6 mice had access to in-cage running wheels (RW) or cages without wheels (NRW) for 16 weeks and were randomized at the end of training to no exercise control (TC) or to treadmill exercise with sacrifice after 90 min of running (TREAD; 30 min, 22 m min(-1); 30 min, 25 m min(-1); 30 min, 28 m min(-1); 2 degrees slope). IL were analyzed for pro-(caspase 3 and 7) and anti-(Bcl-2) apoptotic proteins, endogenous antioxidants (glutathione peroxidase: GPx; catalase: CAT) and the pro-inflammatory cytokine, TNF-alpha. RW mice had higher cytochrome oxidase (p<0.001) and citrate synthase (p<0.01) activities in plantaris and soleus muscles and higher GPx and CAT expression in IL (p<0.05) (indicative of training) compared with NRW mice. TNF-alpha expression was lower (p<0.05) and IL numbers higher (p<0.05) in RW vs. NRW mice. No training effect was observed for apoptotic protein expression, although TREAD resulted in higher caspase and lower Bcl-2. These results suggest that freewheel running in mice for 16 weeks enhances antioxidant and reduces TNF-alpha expression in IL but does not reduce pro-apoptotic protein expression after acute exercise. Results are discussed in terms of implications for inflammatory bowel diseases where apoptotic proteins and TNF-alpha levels are elevated.
 ...
PMID:Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-alpha in intestinal lymphocytes. 1948 47