Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c6 is a soluble metalloprotein located in the periplasmic space and the thylakoid lumen of many cyanobacteria and is known to carry electrons from cytochrome b6f to photosystem I. The CuA domain of cytochrome c oxidase, the terminal enzyme which catalyzes the four-electron reduction of molecular oxygen in the respiratory chains of mitochondria and many bacteria, also has a periplasmic location. In order to test whether cytochrome c6 could also function as a donor for cytochrome c oxidase, we investigated the kinetics of the electron transfer between recombinant cytochrome c6 (produced in high yield in Escherichia coli by coexpressing the maturation proteins encoded by the ccmA-H gene cluster) and the recombinant soluble CuA domain (i.e., the donor binding and electron entry site) of subunit II of cytochrome c oxidase from Synechocystis PCC 6803. The forward and the reverse electron transfer reactions were studied by the stopped-flow technique and yielded apparent bimolecular rate constants of (3.3 +/- 0.3) x 10(5) M(-1) s(-1) and (3.9 +/- 0.1) x 10(6) M(-1) s(-1), respectively, in 5 mM potassium phosphate buffer, pH 7, containing 20 mM potassium chloride and 25 degrees C. This corresponds to an equilibrium constant Keq of 0.085 in the physiological direction (DeltarG'0 = 6.1 kJ/mol). The reduction of the CuA fragment by cytochrome c6 is almost independent on ionic strength, which is in contrast to the reaction of the CuA domain with horse heart cytochrome c, which decreases with increasing ionic strength. The findings are discussed with respect to the potential role of cytochrome c6 as mobile electron carrier in both cyanobacterial electron transport pathways.
 ...
PMID:Kinetics of interprotein electron transfer between cytochrome c6 and the soluble CuA domain of cyanobacterial cytochrome c oxidase. 1547 19

Despite the potential of the inhibitor of apoptosis proteins (IAPs) to block cytochrome c-dependent caspase activation, the critical function of IAPs in regulating mammalian apoptosis remains unclear. We report that the ability of endogenous IAPs to effectively regulate caspase activation depends on the differentiation state of the cell. Despite being expressed at equivalent levels, endogenous IAPs afforded no protection against cytochrome c-induced apoptosis in naive pheochromocytoma (PC12) cells, but were remarkably effective in doing so in neuronally differentiated cells. Neuronal differentiation was also accompanied with a marked reduction in Apaf-1, resulting in a significant decrease in apoptosome activity. Importantly, this decrease in Apaf-1 protein was directly linked to the increased ability of IAPs to stringently regulate apoptosis in neuronally differentiated PC12 and primary cells. These data illustrate specifically how the apoptotic pathway acquires increased regulation with cellular differentiation, and are the first to show that IAP function and apoptosome activity are coupled in cells.
 ...
PMID:Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis. 1550 5

Amyloid-beta (A beta) peptides play a central role in the development of Alzheimer's disease. They are known to induce mitochondrial dysfunction and caspase activation, resulting in apoptosis of neuronal cells. Here we show that human cytoplasmic gelsolin inhibits A beta peptide-induced cell death of neuronally differentiated rat pheochromocytoma (PC-12) cells. We also show that the segment 5 but not 6 of human cytoplasmic gelsolin is the important region responsible for inhibition of A beta-induced cytotoxicity. Mitochondrial dysfunction associated with cell death, membrane potential loss and the release of cytochrome c are all abrogated in the presence of human full-length or segment 5 cytoplasmic gelsolin. Furthermore, RNA interference to reduce expression of endogenous gelsolin in PC-12 cells shows that rat gelsolin act as an inhibitor of A beta cytotoxicity. These results demonstrate that cytoplasmic gelsolin plays a important role in inhibiting Abeta-induced cytotoxicity by inhibiting apoptotic mitochondrial changes. The segment 5 of human cytoplasmic gelsolin is sufficient for the function.
 ...
PMID:Inhibition of Alzheimer's amyloid-beta peptide-induced reduction of mitochondrial membrane potential and neurotoxicity by gelsolin. 1571 43

The physiological transient complex between cytochrome f (Cf) and cytochrome c(6) (Cc(6)) from the cyanobacterium Nostoc sp. PCC 7119 has been analysed by NMR spectroscopy. The binding constant at low ionic strength is 8 +/- 2 mM(-1), and the binding site of Cc(6) for Cf is localized around its exposed haem edge. On the basis of the experimental data, the resulting docking simulations suggest that Cc(6) binds to Cf in a fashion that is analogous to that of plastocyanin but differs between prokaryotes and eukaryotes.
 ...
PMID:An NMR-based docking model for the physiological transient complex between cytochrome f and cytochrome c6. 1587 32

Plastocyanin and cytochrome c6 are two small soluble electron carriers located in the intrathylacoidal space of cyanobacteria. Although their role as electron shuttle between the cytochrome b6f and photosystem I complexes in the photosynthetic pathway is well established, their participation in the respiratory electron transport chain as donors to the terminal oxidase is still under debate. Here, we present the first time-resolved analysis showing that both cytochrome c6 and plastocyanin can be efficiently oxidized by the aa3 type cytochrome c oxidase in Nostoc sp. PCC 7119. The apparent electron transfer rate constants are ca. 250 and 300 s(-1) for cytochrome c6 and plastocyanin, respectively. These constants are 10 times higher than those obtained for the oxidation of horse cytochrome c by the oxidase, in spite of being a reaction thermodynamically more favourable.
 ...
PMID:Respiratory cytochrome c oxidase can be efficiently reduced by the photosynthetic redox proteins cytochrome c6 and plastocyanin in cyanobacteria. 1596 11

Neuropathologies have been associated with neuronal de-differentiation and oxidative susceptibility. To address whether cellular states determines their oxidative vulnerability, we have challenged naive (undifferentiated) and nerve growth factor-induced differentiated pheochromocytoma (PC12) with methylglyoxal (MG), a model of carbonyl stress. MG dose-dependently induced greater apoptosis (24 h) in naive (nPC12) than differentiated (dPC12) cells. This enhanced nPC12 susceptibility was correlated with a high basal oxidized cellular glutathione-to-glutathione disulfide (GSH/GSSG) redox and an MG-induced GSH-to-Disulfide (GSSG plus protein-bound SSG) imbalance. The loss of redox balance occurred at 30 min post-MG exposure, and was prevented by N-acetylcysteine (NAC) that was unrelated to de novo GSH synthesis. NAC was ineffective when added at 1h post-MG, consistent with an early window of redox signaling. This redox shift was kinetically linked to decreased BcL-2, increased Bax, and release of mitochondrial cytochrome c which preceded caspase-9 and -3 activation and poly ADP-ribose polymerase (PARP) cleavage (1-2 h), consistent with mitochondrial apoptotic signaling. The blockade of apoptosis by cyclosporine A supported an involvement of the mitochondrial permeability transition pore. The enhanced vulnerability of nPC12 cells to MG and its relationship to cellular redox shifts will have important implications for understanding differential oxidative vulnerability in various cell types and their transition states.
 ...
PMID:Differential susceptibility of naive and differentiated PC-12 cells to methylglyoxal-induced apoptosis: influence of cellular redox. 1618 Oct 96

The Mn(4) cluster of PS II advances through a series of oxidation states (S states) that catalyze the breakdown of water to dioxygen in the oxygen-evolving complex. The present study describes the engineering and purification of highly active PS II complexes from mesophilic His-tagged Synechocystis PCC 6803 and purification of PS II core complexes from thermophilic wild-type Synechococcus lividus with high levels of the extrinsic polypeptide, cytochrome c (550). The g = 4.1 S(2) state EPR signal, previously not characterized in untreated cyanobacterial PS II, is detected in high yields in these PS II preparations. We present a complete characterization of the g = 4.1 state in cyanobacterial His-tagged Synechocystis PCC 6803 PS II and S. lividus PS II. Also presented are a determination of the stoichiometry of cytochrome c (550) bound to His-tagged Synechocystis PCC 6803 PS II and analytical ultracentrifugation results which indicate that cytochrome c (550) is a monomer in solution. The temperature-dependent multiline to g = 4.1 EPR signal conversion observed for the S(2) state in cyanobacterial PS II with high cytochrome c (550) content is very similar to that previously found for spinach PS II. In spinach PS II, the formation of the S(2) state g = 4.1 EPR signal has been found to correlate with the binding of the extrinsic 17 and 23 kDa polypeptides. The finding of a similar correlation in cyanobacterial PS II with the binding of cytochrome c (550) suggests a functional homology between cytochrome c (550) and the 17 and 23 kDa extrinsic proteins of spinach PS II.
 ...
PMID:Correlation of the cytochrome c (550) content of cyanobacterial Photosystem II with the EPR properties of the oxygen-evolving complex. 1622 16

We have previously reported that cyanobacterial photosystem II (PS II) contains a protein homologous to PsbQ, the extrinsic 17-kDa protein found in higher plant and green algal PS II (Kashino, Y., Lauber, W. M., Carroll, J. A., Wang, Q., Whitmarsh, J., Satoh, K., and Pakrasi, H. B. (2002) Biochemistry 41, 8004-8012) and that it has regulatory role(s) on the water oxidation machinery (Thornton, L. E., Ohkawa, H., Roose, J. L., Kashino, Y., Keren, N., and Pakrasi, H. B. (2004) Plant Cell 16, 2164-2175). In this work, the localization and the function of PsbQ were assessed using the cyanobacterium Synechocystis sp. PCC 6803. From the predicted sequence, cyanobacterial PsbQ is expected to be a lipoprotein on the luminal side of the thylakoid membrane. Indeed, experiments in this work show that upon Triton X-114 fractionation of thylakoid membranes, PsbQ partitioned in the hydrophobic phase, and trypsin digestion revealed that PsbQ was highly exposed to the luminal space of thylakoid membranes. Detailed functional assays were conducted on the psbQ deletion mutant (DeltapsbQ) to analyze its water oxidation machinery. PS II complexes purified from DeltapsbQ mutant cells had impaired oxygen evolution activity and were remarkably sensitive to NH(2)OH, which indicates destabilization of the water oxidation machinery. Additionally, the cytochrome c(550) (PsbV) protein partially dissociated from purified DeltapsbQ PS II complexes, suggesting that PsbQ contributes to the stability of PsbV in cyanobacterial PS II. Therefore, we conclude that the major function of PsbQ is to stabilize the PsbV protein, thereby contributing to the protection of the catalytic Mn(4)-Ca(1)-Cl(x) cluster of the water oxidation machinery.
 ...
PMID:Absence of the PsbQ protein results in destabilization of the PsbV protein and decreased oxygen evolution activity in cyanobacterial photosystem II. 1672 51

Epigallocatechin-3-gallate (EGCG) is a major constituent of green tea polyphenols. This study was aimed to investigate the possible mechanisms of EGCG-mediated inhibition against apoptosis in rat pheochromocytoma PC12 cells by exposure to CoCl(2). Exposure to CoCl(2) caused the generation of ROS and induced cell death with appearance of apoptotic morphology and DNA fragmentation. However, EGCG rescued the loss of viability in the cells exposed to CoCl(2) and led the reduction of DNA fragmentation and sub-G(1) fraction of cell cycle. Also, EGCG attenuated the CoCl(2)-induced disruption of mitochondrial membrane potential (DeltaPsim), release of cytochrome c from the mitochondria to cytosol and abolished the CoCl(2)-stimulated activities of the caspase cascades, caspase-9 and caspase-3. In addition, EGCG ameliorated the increase in the Bax to Bcl-2 ratio, a marker of apoptosis proceeding, induced by CoCl(2) treatment. Taken together, the present results suggest that EGCG inhibit the CoCl(2)-induced apoptosis of PC12 cells through the mitochondria-mediated apoptosis pathway involved in modulating the Bcl-2 family.
 ...
PMID:Inhibition by epigallocatechin gallate of CoCl2-induced apoptosis in rat PC12 cells. 1724 Apr 4

Alterations in lipid metabolism play an integral role in neuronal death in cerebral ischemia. Here we used an in vitro model, oxygen-glucose deprivation (OGD) of rat pheochromocytoma (PC12) cells, and analyzed changes in phosphatidylcholine (PC) and sphingomyelin (SM) metabolism. OGD (4-8 h) of PC12 cells triggered a dramatic reduction in PC and SM levels, and a significant increase in ceramide. OGD also caused increases in phosphatidylcholine-phospholipase C (PC-PLC) and phospholipase D (PLD) activities and PLD2 protein expression, and reduction in cytidine triphosphate:phosphocholine cytidylyltransferase-alpha (CCTalpha, the rate-limiting enzyme in PC synthesis) protein expression and activity. Phospholipase A2 activity and expression were unaltered during OGD. Increased neutral sphingomyelinase activity during OGD could account for SM loss and increased ceramide. Surprisingly, treatment with PC-PLC inhibitor tricyclodecan-9-yl potassium xanthate (D609) aggravated cell death in PC12 cells during OGD. D609 was cytotoxic only during OGD; cell death could be prevented by inclusion of sera, glucose or oxygen. During OGD, D609 caused further loss of PC and SM, depletion of 1,2-diacylglycerol (DAG), increase in ceramide and free fatty acids (FFA), cytochrome c release from mitochondria, increases in intracellular Ca2+ ([Ca2+]i), poly-ADP ribose polymerase (PARP) cleavage and phosphatidylserine externalization, indicative of apoptotic cell death. Exogenous PC during OGD in PC12 cells with D609 attenuated PC, SM loss, restored DAG, attenuated ceramide levels, decreased cytochrome c release, PARP cleavage, annexin V binding, attenuated the increase in [Ca2+]i, FFA release, and significantly increased cell viability. Exogenous PC may have elicited these effects by restoring membrane PC levels. A tentative scheme depicting the mechanism of action of D609 (inhibiting PC-PLC, SM synthase, PC synthesis at the CDP-choline-1,2-diacylglycerol phosphocholine transferase (CPT) step and causing mitochondrial dysfunction) has been proposed based on our observations and literature.
 ...
PMID:Effect of tricyclodecan-9-yl potassium xanthate (D609) on phospholipid metabolism and cell death during oxygen-glucose deprivation in PC12 cells. 1743 80


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