Paroxetine binding and activation of phosphofructokinase implicates energy metabolism in antidepressant mode of action

Intracellular levels of ATP, GTP, and hexose phosphates have been determined in HeLa cells at intervals after exposure to saturating doses of diphtheria toxin. Toxin causes no significant change in the level of any of these phosphorylated intermediates either in the presence or absence of glucose over a period of at least 5 to 6 hours. It is concluded that the inhibition of protein synthesis which occurs in HeLa cells at about 2 hours after the addition of saturating doses of toxin, does not result from an effect of toxin on energy metabolism.

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Insights from the proteome profile of Phytophthora capsici in response to the novel fungicide SYP-14288

PeerJ ◽

10.7717/peerj.7626 ◽

2019 ◽

Vol 7 ◽

pp. e7626 ◽

Cited By ~ 6

Author(s):

Meng Cai ◽

Zhiwen Wang ◽

Xiaoxia Ni ◽

Yanhua Hou ◽

Qin Peng ◽

...

Keyword(s):

Energy Metabolism ◽

Mode Of Action ◽

Crop Production ◽

Plant Pathogens ◽

The Novel ◽

Compensatory Mechanisms ◽

Oxidoreductase Activity ◽

Altered Expression ◽

Proteomic Data ◽

Fungal Plant Pathogens

Phytophthora capsica is a destructive oomycete plant pathogen that causes huge losses to crop production worldwide. However, the novel fungicide SYP-14288 has shown excellent activity against various stages of the oomycete life cycle as well against fungal plant pathogens. The current study utilized isobaric tags for relative and absolute quantitation technology to generate proteome profiles of P. capsici in the presence or absence of SYP-14288 in order to gain a greater understanding of the SYP-14288 mode of action. A total of 1,443 individual proteins were identified during the investigation, of which 599 were considered to have significantly altered expression. Further investigation using Cluster of Orthologous Groups of proteins analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated most of the proteins with altered expression were associated with carbohydrate metabolism, energy metabolism and their downstream biological functions, especially with regard to oxidoreductase activity and subsequent adenosine triphosphate (ATP) production associated pathways. Quantitative expression analysis using qRT-PCR validated the proteomic data. These results seem to indicate that SYP-14288 treatment caused a shift in energy metabolism that resulted in the activation of compensatory mechanisms affecting carbohydrate and lipid metabolism. The study also found evidence that the up-regulation of transmembrane transporters and proteins associated with stress response might also be coopted to compensate for the disrupted proton gradient and other downstream effects. Taken together these results provide strong evidence that SYP-14288 has a similar mode of action to the oxidative phosphorylation uncoupler Fluazinam but further investigation, including molecular studies, is required to completely characterize the SYP-14288 mode of action in P. capsici. However, the proteomic data collected in the current study does provide important insight into the overall effect of SYP-14288 in P. capsici, which could be useful for the registration and application of this novel fungicide.

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Effects of 5-5'-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine on the Ultrastructure and Chemical Composition of Rat Liver

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066917 ◽

1971 ◽

Vol 29 ◽

pp. 570-571

Author(s):

E. A. Elfont ◽

R. B. Tobin ◽

D. G. Colton ◽

M. A. Mehlman

Keyword(s):

Chemical Composition ◽

Rat Liver ◽

Future Study ◽

Mode Of Action ◽

Liver Mitochondria ◽

Rat Liver Mitochondria ◽

Effective Inhibitor ◽

Biochemical Effects ◽

Glycerophosphate Dehydrogenase ◽

Stimulation Of

Summary5,-5'-diphenyl-2-thiohydantoin (DPTH) is an effective inhibitor of thyroxine (T4) stimulation of α-glycerophosphate dehydrogenase in rat liver mitochondria. Because this finding indicated a possible tool for future study of the mode of action of thyroxine, the ultrastructural and biochemical effects of DPTH and/or thyroxine on rat liver mere investigated.Rats were fed either standard or DPTH (0.06%) diet for 30 days before T4 (250 ug/kg/day) was injected. Injection of T4 occurred daily for 10 days prior to sacrifice. After removal of the liver and kidneys, part of the tissue was frozen at -50°C for later biocheailcal analyses, while the rest was prefixed in buffered 3.5X glutaraldehyde (390 mOs) and post-fixed in buffered 1Z OsO4 (376 mOs). Tissues were embedded in Araldlte 502 and the sections examined in a Zeiss EM 9S.Hepatocytes from hyperthyroid rats (Fig. 2) demonstrated enlarged and more numerous mitochondria than those of controls (Fig. 1). Glycogen was almost totally absent from the cytoplasm of the T4-treated rats.

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Mitochondrial matrix calcium ions regulate energy production in myocardium: A cytochemical study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100134429 ◽

1990 ◽

Vol 48 (2) ◽

pp. 166-167

Author(s):

W.A. Jacob ◽

R. Hertsens ◽

A. Van Bogaert ◽

M. De Smet

Keyword(s):

Energy Metabolism ◽

Calcium Ions ◽

Energy Production ◽

Regulation Of Respiration ◽

Free Calcium ◽

Mitochondrial Matrix ◽

Cytochemical Study ◽

Nmr Techniques

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.

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