Destabilizing effects of fructose‐1,6‐bisphosphate on membrane bilayers

Ehringer, William D.; Su, Susan; Chiang, Benjamin; Stillwell, William; Chien, Sufan

doi:10.1007/s11745-002-0975-2

Cited by 15 publications

(7 citation statements)

References 30 publications

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“…Another study demonstrated that cells and tissues treated with labelled [C 13 ]FBP produce [C 13 ]lactate, which indicates that exogenously given FBP can participate in the glycolytic pathway to reestablish ATP pool inside the cells [28]. One hypothesis is that FBP could briefly interact with calcium that stabilizes bilayer lipid membrane, leading to an increase in membrane fluidity that would allow FBP to cross it through passive diffusion [29]. Further, the permeability of FBP through a dicarboxylate transporter was reported, although only the linear form of FBP, a small fraction of total FBP, can use this system [30].…”

Section: Discussionmentioning

confidence: 99%

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

et al. 2019

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Pulmonary fibrosis (PF) is the result of chronic injury where fibroblasts become activated and secrete large amounts of extracellular matrix (ECM), leading to impaired fibroblasts degradation followed by stiffness and loss of lung function. Fructose-1,6-bisphosphate (FBP), an intermediate of glycolytic pathway, decreases PF development, but the underlying mechanism is unknown. To address this issue, PF was induced in vivo using a mouse model, and pulmonary fibroblasts were isolated from healthy and fibrotic animals. In PF model mice, lung function was improved by FBP as revealed by reduced collagen deposition and downregulation of ECM gene expression such as collagens and fibronectin. Fibrotic lung fibroblasts (FLF) treated with FBP for 3 days in vitro showed decreased proliferation, contraction, and migration, which are characteristic of myofibroblast to fibroblast phenotype reversal. ECM-related genes and proteins such as collagens, fibronectin and α-smooth muscle actin, were also downregulated in FBP-treated FLF. Moreover, matrix metalloproteinase (MMP) 1, responsible for ECM degradation, was produced only in fibroblasts obtained from healthy lungs (HLF) and FBP did not alter its expression. On the other hand, tissue inhibitor of metalloproteinase (TIMP)-1, a MMP1 inhibitor, and MMP2, related to fibroblast tissue-invasion, were predominantly produced by FLF and FBP was able to downregulate its expression. These results demonstrate that FBP may prevent bleomycin-induced PF development through reduced expression of collagen and other ECM components mediated by a reduced TIMP-1 and MMP2 expression.

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Section: Discussionmentioning

confidence: 99%

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

et al. 2019

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“…Fru-1,6-P 2 has been reported to enter myocytes and large unilamellar vesicles (28,29), although the mechanism is controversial. Instead of using Fru-1,6-P 2 , we used the cell-permeable analog 2,5-AM, which enters cells and is phosphorylated to yield 2,5-AM-ol bisphosphate (30), which accumulates in the cytosol because it is not metabolized.…”

Section: Volume 286 • Number 23 • June 10 2011mentioning

confidence: 99%

Phosphate and Succinate Use Different Mechanisms to Inhibit Sugar-induced Cell Death in Yeast

Lee

Burlet

Galiano

et al. 2011

Journal of Biological Chemistry

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Stationary-phase Saccharomyces cerevisiae cells transferred from spent rich media into water live for weeks, whereas the same cells die within hours if transferred into water with 2% glucose in a process called sugar-induced cell death (SICD). Our hypothesis is that SICD is due to a dysregulated Crabtree effect, which is the phenomenon whereby glucose transiently inhibits respiration and ATP synthesis. We found that stationary-phase cells in glucose/water consume 21 times more O 2 per cell than exponential-phase cells in rich media, and such excessive O 2 consumption causes reactive oxygen species to accumulate. We also found that inorganic phosphate and succinate protect against SICD but by different mechanisms. Phosphate protects by triggering the synthesis of Fru-1,6-P 2 , which inhibits respiration in isolated mitochondria. Succinate protects in wild-type cells but fails to protect in dic1⌬ cells. DIC1 codes for a mitochondrial inner membrane protein that exchanges cytosolic succinate for matrix phosphate. We propose that succinate depletes matrix phosphate, which in turn inhibits respiration and ATP synthesis. In sum, restoring the Crabtree effect, whether with phosphate or succinate, protects cells from SICD.Saccharomyces cerevisiae cells undergo glucose-induced inhibition of respiration and oxidative phosphorylation and a parallel up-regulation of both glycolysis and glucose uptake by a short-term mechanism called the "Crabtree effect" (1-5). The Crabtree effect is a reversible process, and the precise mechanism of this phenomenon is controversial (6 -8). In addition to the down-regulation of genes involved in respiration and oxidative phosphorylation by glucose (9, 10), the Crabtree effect may involve competition between mitochondrial respiratory enzymes and glycolytic enzymes for ADP and inorganic phosphate (11, 12), changes in the permeability of the outer mitochondrial membrane (8), and the accumulation of certain metabolic intermediates, especially Fru-1,6-P 2 (6).The possibility that Fru-1,6-P 2 mediates the Crabtree effect was shown in a recent study that used mitochondria isolated from Crabtree-positive and Crabtree-negative yeast (6).Notably, Fru-1,6-P 2 decreased the rate of O 2 consumption in mitochondria isolated from the Crabtree-positive yeast (S. cerevisiae), but not that in mitochondria isolated from the Crabtree-negative yeast (Candida utilis). Such a result indicates that Fru-1,6-P 2 mediates the Crabtree effect.Although glucose triggers the Crabtree effect when yeast cells are cultured in rich media, glucose in water is very toxic to cells, especially stationary-phase (G 0 ) cells. When stationaryphase cells are shifted into 2% glucose or fructose in water, the cells begin to bud but then rapidly lose viability within a few hours (13,14). The cells undergo an apoptotic death triggered by reactive oxygen species (ROS) 2 accumulation (15). ROS accumulation suggests that the respiratory pathway in mitochondria is turned on rather than repressed. The sugar-induced cell death (SICD) is indep...

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“…Thus, during hemorrhagic shock, all energy-dependent processes including membrane transport are compromised severely resulting in an osmotic imbalance leading to cellular edema. Replenishing ATP by means of resuscitation in hemorrhagic shock, however, has been ineffective due both to its inability to pass the cell membrane in large quantities as well as its short half-life in circulation [25–31]. Administration of glutamine (a precursor of ATP), lipid encapsulated ATP, pyruvate, and crocetin have been effective in restoring energy and decreasing cellular damage after hemorrhagic shock in animal models [5,32–34].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of fatty acid synthase with C75 decreases organ injury after hemorrhagic shock

Kuncewitch

Yang

Jacob

et al. 2016

Surgery

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Background Hemorrhagic shock is the primary cause of morbidity and mortality in the intensive care units in patients under the age of 35. Several organs including the lungs are seriously affected due to the hemorrhagic shock and inadequate resuscitation. Excess free fatty acids have shown to trigger inflammation in various disease conditions. C75 is a small compound that inhibits fatty acid synthase, a key enzyme in the control of fatty acid metabolism that also stimulates fatty acid oxidation. We hypothesized that C75 treatment would be protective against hemorrhagic shock. Methods Adult, male, Sprague-Dawley rats were cannulated with a femoral artery catheter and subjected to controlled bleeding. Blood was shed to maintain a mean arterial pressure of 30 mm Hg for 90 min, then resuscitated over 30 min with a crystalloid volume equal to twice the volume of shed blood. Fifteen minutes into the 30 min resuscitation, the rats received either intravenous infusion of C75 (1 mg/kg BW) or vehicle (20% DMSO). Blood and tissue samples were collected 6 h after resuscitation (i.e., 7.5 h after hemorrhage) for analysis. Results After hemorrhage and resuscitation, C75 treatment decreased the increase in serum free fatty acids by 48%, restored adenosine triphosphate (ATP) levels, and stimulated carnitine palmitoyl transferase-1 (CPT-1) activity. Administration of C75 decreased serum levels of markers of injury (AST, lactate, and LDH) by 38%, 32%, and 78%, respectively. Serum creatinine and blood urea nitrogen (BUN) were also significantly decreased by 38% and 40%, respectively. These changes correlated with decreases in neutrophil infiltration in the lung, evidenced by decreases in Gr-1-stained cells and myeloperoxidase activity and improved lung histology. Finally, administration of C75 decreased pulmonary mRNA levels of COX-2 and IL-6 by 87% and 65%, respectively. Conclusions Administration of C75 after hemorrhage and resuscitation decreased the increase in serum FFA, decreased markers of tissue injury, downregulated the expression of inflammatory mediators, and decreased neutrophil infiltration and lung injury. Thus, the dual action of inhibiting fatty acid synthesis and stimulating fatty acid oxidation by C75 could be developed as a promising adjuvant therapy strategy to protect against hemorrhagic shock.

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Destabilizing effects of fructose‐1,6‐bisphosphate on membrane bilayers

Cited by 15 publications

References 30 publications

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

Phosphate and Succinate Use Different Mechanisms to Inhibit Sugar-induced Cell Death in Yeast

Inhibition of fatty acid synthase with C75 decreases organ injury after hemorrhagic shock

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