Respiratory changes induced by guanidines and cations in submitochondrial particles

Lotina, Blas; Gómez‐Puyou, Marietta Tuena de; Gómez‐Puyou, Armando

doi:10.1016/0003-9861(73)90484-0

Cited by 18 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The significance of the upregulation of Tribbles‐3 (which has not been validated using QPCR) is unclear, but this gene was found recently to be upregulated in 3T3‐L1 adipocytes in response to reductions in available glucose and was suggested to be involved in cell‐survival in response to glucose deprivation ( Yacoub Wasef et al , 2006 ). This may relate to the previously demonstrated inhibitory effect of galegine on mitochondrial respiration ( Lotina et al , 1973 ), which could be the mechanism whereby it activates AMPK, as indicated above for the biguanides. In this context, however, we were unable to detect any significant effect of galegine on the expression of genes concerned with oxidative phosphorylation (for example, NADPH‐ubiquinone dehydrogenase, succinate dehydrogenase complex, ATP synthase) in 3T3‐L1 adipocytes.…”

Section: Discussionmentioning

confidence: 56%

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice

Mooney

Fogarty

Stevenson

et al. 2008

British J Pharmacology

View full text Add to dashboard Cite

Background and purpose: Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. Experimental approach: Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. Key results: Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, galegine (50 mM-3 mM) stimulated glucose uptake. Galegine (1-300 mM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetylCoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 mM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 mM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. Conclusions and implications: Activation of AMPK can explain many of the effects of galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of galegine on body weight.

show abstract

Section: Discussionmentioning

confidence: 56%

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice

Mooney

Fogarty

Stevenson

et al. 2008

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…A competition between the action of monovalent cations and octylguanidine has been reported (12,13,24,27). A LineweaverBurk plot of 86Rb+ uptake at various concentration of 86Rb+ is shown in Figure 2.…”

Section: Resultsmentioning

confidence: 87%

“…In this work, a possible action of various alkylguanidines on the absorption of K+ by excised barley roots has been explored. The effect of alkylguanidines on K+ uptake in plants was studied because these lipophilic cations (their pKa is around 12) have been shown to inhibit numerous metal ion-dependent systems (1,2,12,13,16,23,24,(27)(28)(29) tinuously aerated distilled H20, and rinsed again 3 times with distilled H20. Seedlings were grown essentially as described by Epstein (4).…”

mentioning

confidence: 99%

Alkylguanidines as Inhibitors of K⁺ Transport in Isolated Barley Roots

Lepe¹,

Avila²

1975

Plant Physiol.

View full text Add to dashboard Cite

It has beeii shown that plants can accunmulate K+ through an energy-dependent process. The effect of alkylguanidines, in particular octylguanidine on the uptake of 86Rb+ by excised barley roots (Hordeum vulgare var. Apizaco LV-72), has been studied. s6Rb+ was used as tracer of K+. The uptake of 86Rb+ which is linear with time and shows saturation kinetics is inhibited by octylguanidine. Half-maximal (5,6,14,15).Little is known with respect to the molecular events that occur during K+ translocation. It has been suggested that a membranebound ATPase participates in the process (8,9,18,20,22,25) and that the uptake of K+ involves the combination of a hypothetical carrier with the ion in such a way that the intermediate ion-carrier complex that is formed on the outer part of the membrane breaks down irreversibly on the internal side of the membrane releasing the ion inside the cell (3,6,10,11). In this work, a possible action of various alkylguanidines on the absorption of K+ by excised barley roots has been explored. The effect of alkylguanidines on K+ uptake in plants was studied because these lipophilic cations (their pKa is around 12) have been shown to inhibit numerous metal ion-dependent systems (1,2,12,13,16,23,24,(27)(28)(29) tinuously aerated distilled H20, and rinsed again 3 times with distilled H20. Seedlings were grown essentially as described by Epstein (4). The seeds were placed on a plastic screen covered with cheesecloth which was supported by a 7-liter plastic tank containing 5 liters of 0.5 mm CaSO4; the corners of the cheesecloth were dipped into the solution. The tank was placed in the dark and covered with a plastic cover. The temperature was 24 C + 3 and vigorous aeration was provided.Roots from 6-day-old seedlings were used for the absorption experiments. The roots were cut in 2-cm segments (the 3-cm basal portions and 5-cm apical portions of the roots were discarded) and washed 3 times with ice-cold distilled H20. The tissue prepared in this form is a highly homogeneous material. Batches of 16 segments were maintained in distilled H20 until the experiment was initiated. The uptake experiments were carried out by incubating barley roots in 4 ml of a mixture that contained 20 mm maleic buffer (pH 6), 0.05 mm CaSO4, and different concentrations of the indicated alkylguanidines and RbCl according to the experiment. Experiments on the ion absorption by excised tissues of higher plants have shown that potassium and rubidium behave virtually as isotopes of the same element (21). Therefore, l6Rb+ was used as a radioactive analog of K+. The incubation medium was maintained at 30 C and continuously shaken in a Dubnoff incubator. The solution was equilibrated for a 10-min period prior to the addition of the roots. At the times indicated in the respective figures (see under "Results"), the solution was decanted, and the roots were rinsed for 30 sec with a mixture of 30 ml of ice-cold 0.5 mm CaSO4 and 5 mm RbCl to eliminate adsorbed lGRb+. Subsequently the roots were washed for 30 min in 15 ml...

show abstract

Evaluation of suppressor behavior of guanidine‐derived metformin and galegine as novel potential drugs for cancer treatment: an in silico study

Behrouzi Varjovi,

Asghari‐Zakaria,

Hosseinzadeh

2024

Biotech and App Biochem

View full text Add to dashboard Cite

There are some natural products from plants that can prevent and treat disease. Metformin, a derivative of galegine, is the basic drug to treat diabetes. Moreover, this molecule has anticancer properties that inhibit cancer cell growth and proliferation. In this study, the main interactions of galegine and metformin with various cancer‐involved proteins, including mitochondrial alpha‐glycerophosphate dehydrogenase, yeast NADH dehydrogenase, and transforming growth factor‐β1, were surveyed by molecular docking and molecular dynamics simulations. The results showed that each of the proteins makes complexes with the ligands via favorable non‐bonded interactions, especially hydrogen bond interactions. There is greater stability for complexes containing galegine based on the root mean square deviation results. The higher structure compactness is also found in galegine receptors than in metformin receptors. Calculation of ΔGbinding, using the MM/PBSA methodology, shows that the binding energy values for metformin and galegine in interaction with each of the receptors are almost the same, and galegine has similar binding properties with metformin in interaction with the studied protein receptors. Therefore, galegine, a natural ingredient with better binding properties to cancer‐involved proteins than metformin (with various side effects), can be applied as a new drug for cancer treatment.

show abstract

Respiratory changes induced by guanidines and cations in submitochondrial particles

Cited by 18 publications

References 18 publications

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice

Alkylguanidines as Inhibitors of K⁺ Transport in Isolated Barley Roots

Evaluation of suppressor behavior of guanidine‐derived metformin and galegine as novel potential drugs for cancer treatment: an in silico study

Contact Info

Product

Resources

About

Respiratory changes induced by guanidines and cations in submitochondrial particles

Cited by 18 publications

References 18 publications

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice

Alkylguanidines as Inhibitors of K+ Transport in Isolated Barley Roots

Evaluation of suppressor behavior of guanidine‐derived metformin and galegine as novel potential drugs for cancer treatment: an in silico study

Contact Info

Product

Resources

About

Alkylguanidines as Inhibitors of K⁺ Transport in Isolated Barley Roots