Inhibition of Mitochondrial Electron Transfer in Rats by Ethanethiol and Methanethiol

1979 ◽  
Vol 56 (2) ◽  
pp. 147-156 ◽  
Author(s):  
T. Vahlkamp ◽  
A. J. Meijer ◽  
J. Wilms ◽  
R. A. F. M. Chamuleau
Keyword(s):  
Electron Transfer ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Rat Hepatocytes ◽  
Rat Liver Mitochondria ◽  
Dimethyl Sulphide ◽  
Submitochondrial Particles ◽  
Isolated Rat Hepatocytes ◽  
The Difference ◽  
Isolated Rat

1. We have investigated the effects of ethanethiol, methanethiol and dimethyl sulphide on some metabolic processes of isolated rat hepatocytes, isolated mitochondria from liver and brain and ox-heart submitochondrial particles. 2. Ethanethiol, but not dimethyl sulphide, inhibited both gluconeogenesis and ureogenesis from various substrates in rat hepatocytes, depressed cellular ATP content and caused an increased reduction of the mitochondria. 3. Ethanethiol inhibited respiration in isolated rat-liver mitochondria with several substrates, both in the presence of ADP and phosphate or in the presence of an uncoupling agent. Ethanethiol also inhibited respiration in isolated rat-brain mitochondria. Dimethyl sulphide was much less effective in inhibiting mitochondrial respiration. 4. In ox-heart submitochondrial particles ethanethiol inhibited electron transfer between cytochrome c and oxygen. 5. Purified cytochrome c oxidase was inhibited by ethanethiol in a non-competitive manner. 6. Methanethiol inhibited cytochrome c oxidase and was an effective inhibitor of mitochondrial electron transfer, both in liver and brain. 7. The difference in inhibitory properties between ethanethiol, methanethiol and dimethyl sulphide observed in our experiments coincides with the difference in potency to elicit coma in rats. We suggest that inhibition of mitochondrial electron transfer by mercaptans may be relevant to the mechanism by which energy production in brain is depressed during hepatic coma.

scholarly journals Biosynthesis of cytochrome c oxidase in isolated rat hepatocytes

FEBS Letters ◽  
1980 ◽  
Vol 115 (1) ◽  
pp. 95-99 ◽  
Author(s):  
E. Hundt ◽  
M. Trapp ◽  
B. Kadenbach
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

Hepatotoxic effect of (+)usnic acid from Usnea siamensis Wainio in rats, isolated rat hepatocytes and isolated rat liver mitochondria

2004 ◽  
Vol 90 (2-3) ◽  
pp. 381-387 ◽  
Author(s):  
Pornpen Pramyothin ◽  
Withaya Janthasoot ◽  
Nushjira Pongnimitprasert ◽  
Siriwan Phrukudom ◽  
Nijsiri Ruangrungsi
Keyword(s):  
Rat Liver ◽  
Usnic Acid ◽  
Rat Hepatocytes ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat Liver ◽  
Hepatotoxic Effect ◽  
Isolated Rat

scholarly journals Kinetics of inhibition of purified and mitochondrial cytochrome c oxidase by psychosine (β-galactosylsphingosine)

1993 ◽  
Vol 290 (1) ◽  
pp. 139-144 ◽  
Author(s):  
C E Cooper ◽  
M Markus ◽  
S P Seetulsingh ◽  
J M Wrigglesworth
Keyword(s):  
Cytochrome C ◽  
Cytochrome Oxidase ◽  
Cytochrome C Oxidase ◽  
Rat Liver ◽  
Liver Mitochondria ◽  
Slow Phase ◽  
Rat Liver Mitochondria ◽  
Mitochondrial Cytochrome ◽  
Submitochondrial Particles ◽  
Bovine Heart

1. Psychosine (beta-galactosylsphingosine) is the toxic agent in Krabbe's disease (globoid cells leukodystrophy). It inhibits purified bovine heart mitochondrial cytochrome c oxidase; there is a rapid phase of inhibition (complete within 10-15 s) and a slower phase (complete within 10-15 min). Both phases are also seen in rat liver mitochondria. IC50 is about 200 microM psychosine in the purified enzyme and less than 20 microM in mitochondria. Psychosine inhibition is due to binding to cytochrome oxidase, not cytochrome c. 2. Bovine heart submitochondrial particles show inhibition similar to rat liver mitochondria. However, although proteoliposomes containing bovine heart cytochrome oxidase show an identical fast phase, they have no noticeable slow phase of inhibition. Addition of phospholipid liposomes to submitochondrial particles relieved the majority of psychosine inhibition, consistent with the removal of those molecules binding in the slow phase. Psychosine can inhibit cytochrome oxidase molecules facing in either direction in proteoliposomes and submitochondrial particles, suggesting that it can rapidly interact with both sides of a membrane when added externally. 3. At high ionic strength, the presence of psychosine decreases the Vmax. of cytochrome oxidase with little effect on the Km for cytochrome c. This non-competitive inhibition suggests that the psychosine-enzyme complex is kinetically inactive and not labile over the time course of the assay. Psychosine does not inhibit the reduction of haem a or haem a3 by artificial electron donors, but does inhibit the reduction of haem a by cytochrome c.

scholarly journals Import of rat liver mitochondrial transhydrogenase

1988 ◽  
Vol 252 (3) ◽  
pp. 833-836 ◽  
Author(s):  
L N Y Wu ◽  
I M Lubin ◽  
R R Fisher
Keyword(s):  
Rat Liver ◽  
Proteinase Inhibitors ◽  
Rat Hepatocytes ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Translation System ◽  
Isolated Rat Hepatocytes ◽  
Matrix Fraction ◽  
Translation Mixture ◽  
Isolated Rat

The biosynthesis of pyridine dinucleotide transhydrogenase has been studied in isolated rat hepatocytes and in a rabbit reticulocyte-lysate translation system supplemented with either intact isolated rat liver mitochondria or the soluble matrix fraction from isolated mitochondria. In intact hepatocytes, the transhydrogenase precursor was short-lived in the cytosol and was efficiently imported into the membranous fraction. When the cell-free translation mixture was incubated with intact mitochondria, the transhydrogenase precursor was processed to the mature form, to an extent that depended on the amount of added mitochondria. Incubation of the translation mixture with the soluble mitochondria matrix fraction converted the precursor to a mature-sized protein with 75% efficiency, this being blocked by various proteinase inhibitors such as EDTA, 1,10-phenanthroline and leupeptin.

Inhibition of cytochrome-c oxidase activity during prolonged hypoxia

1995 ◽  
Vol 268 (6) ◽  
pp. L918-L925 ◽  
Author(s):  
N. Chandel ◽  
G. R. Budinger ◽  
R. A. Kemp ◽  
P. T. Schumacker
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Acute Hypoxia ◽  
Rat Hepatocytes ◽  
Cellular Respiration ◽  
Rat Liver Mitochondria ◽  
Low Oxygen ◽  
Isolated Mitochondria ◽  
Critical Tension ◽  
Significant Difference

During acute (< 30 min) hypoxia, cellular respiration is independent of the O2 concentration as long as PO2 remains above a critical value (5–10 Torr). Similarly, state 3 respiration by isolated mitochondria is independent of PO2 above a critical tension of 2–4 Torr. However, rat hepatocytes demonstrate a reversible suppression of respiration and an increase in NAD(P)H concentration during prolonged (2–24 h), but not acute hypoxia [P. T. Schumacker, N. Chandel, and A. G. N. Augusti. Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L395–L402, 1993]. This study tested whether respiration is similarly inhibited in isolated mitochondria exposed to low PO2 for prolonged periods and whether cytochrome-c oxidase participates in this response. Coupled rat liver mitochondria were incubated under low oxygen conditions (PO2 < 2 Torr) for 2 h. State 3 respiration after reoxygenation to PO2 = 20 Torr was then compared with the value obtained subsequently at 100 Torr. Using succinate and ADP as substrates, we determined that state 3 respiration at 20 Torr was 61.0 +/- 8.4% of the subsequent value at 100 Torr (P < 0.05). By contrast, control mitochondria reoxygenated to 100 Torr first and 20 Torr subsequently showed no significant difference at the two O2 tensions (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition by dicyclohexylcarbodiimide of ATP synthesis in isolated rat hepatocytes

1984 ◽  
Vol 4 (3) ◽  
pp. 189-194 ◽  
Author(s):  
S. Emami ◽  
A. Lodola ◽  
M. Partis ◽  
D. R. Sanadi
Keyword(s):  
Atp Synthesis ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Submitochondrial Particles ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

Dicyclohexylcarbodiimide (DCCD) inhibits, by 50%, ATP synthesis in isolated hepatocytes. This inhibition is associated with DCCD-binding to a proteolipid fraction present in submitochondrial particles.

scholarly journals Mitochondrial K+ as modulator of Ca2+-dependent cytotoxicity in hepatocytes. Novel application of the K+-sensitive dye PBFI (K+-binding benzofuran isophthalate) to assess free mitochondrial K+ concentrations

1994 ◽  
Vol 299 (2) ◽  
pp. 539-543 ◽  
Author(s):  
J P Zoeteweij ◽  
B van de Water ◽  
H J de Bont ◽  
J F Nagelkerke
Keyword(s):  
Mitochondrial Membrane ◽  
Rat Hepatocytes ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
High Increase ◽  
Isolated Rat Hepatocytes ◽  
Permeabilized Cells ◽  
K Concentration ◽  
Isolated Rat

In isolated rat hepatocytes a sustained high increase in intracellular free Ca2+ ([Ca2+]i), induced by extracellular ATP, is associated with mitochondrial dysfunction and cell death. The Ca(2+)-induced effects are Pi-dependent and less severe when the intracellular K+ content is low. In this study, the involvement of mitochondrial K+ processing in Ca(2+)-induced loss of mitochondrial membrane potential (MMP) and viability was investigated. The recently introduced K(+)-sensitive dye PBFI (K(+)-binding benzofuran isophthalate) has been used in combination with video-microscopy to assess intramitochondrial free K+ concentration ([K+]mito) in rat liver mitochondria in situ. After rapid permeabilization of the plasma membrane to remove cytosolic PBFI, the remaining PBFI was localized in mitochondria, and a ‘resting’ [K+]mito of approx. 15 mM could be measured. Increased [K+]mito levels were measured after induction of a prolonged increase in [Ca2+]i by ATP. Much lower [K+]mito, more comparable with control levels, were observed when intracellular K+ was depleted by omission of extracellular K+. In permeabilized cells the Ca(2+)-induced, Pi-dependent, dissipation of the MMP was markedly delayed in the absence of K+. These observations suggest involvement of [K+]mito as modulating agent in Ca(2+)-induced cytotoxicity in hepatocytes.

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