Phosphoenolpyruvate, a glycolytic intermediate, as a cytoprotectant and antioxidant in ex-vivo cold-preserved mouse liver: a potential application for organ preservation

Abstract

PEP significantly attenuated the injury, oxidative stress and ATP depletion in liver during cold preservation. The antioxidative potential of PEP was confirmed by in-vitro examination. We suggest that PEP acts as a glycolytic intermediate and antioxidant, and is particularly useful as an organ preservation agent in clinical transplantation.

Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor-bearing hosts through prevention of ROS-mediated apoptosis

“…In a previous study, PEP was shown to significantly attenuate the injury, oxidative stress and ATP depletion in livers during cold preservation for organ transplantation. 36 This glycolytic intermediate was shown to accumulate in GM-CSF-induced MDSCs (data not shown) and prevent ROS production and apoptosis of MDSCs during the blockade of glycolysis in our studies. This result strongly suggests that the upregulation of glycolysis is a way for MDSCs to accumulate enough PEP for prevention of excess ROS production and maintenance of their survival.…”

Evaluation of Three-Dimensional Cultured HepG2 Cells in a Nano Culture Plate System: an In Vitro Human Model of Acetaminophen Hepatotoxicity

“…APAP-induced viability of HepG2 cells was evaluated by a cell viability assay and by the calcein-acetomethoxy (calcein-AM) and propidium iodide (PI) (which stain viable and dead cells, respectively) dual-staining assay as previously described (21). Cell viability was measured using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, namely, the water-soluble tetrazolium salt (WST-8) assay, using a Cell Counting Kit (Dojindo Laboratories) according to the manufacturer's protocol.…”

Comparative Effects of Phosphoenolpyruvate, a Glycolytic Intermediate, as an Organ Preservation Agent with Glucose and N-Acetylcysteine against Organ Damage during Cold Storage of Mouse Liver and Kidney

“…The ex vivo cold storage liver model was developed as previously described [11]. Phosphate-buffered saline (PBS, pH 7.4), 1 mM, 10 mM, and 100 mM PEP, 100 mM glucose, and 10 mM NAC dissolved in PBS were used as the preservation solutions.…”

“…It has been reported that PEP improves the energy status of the heart [7] and skeletal muscle [8] after ischemia and that of the liver after ischemia-reperfusion [9]. Recently, we demonstrated that PEP has scavenging potentials against reactive oxygen species, such as hydroxyl radicals and hydrogen peroxide, which contribute to pathophysiological damage as inducers of oxidative stress in a diseased state [10, 11]. We also elucidated that PEP drastically attenuates cellular injury induced by hydrogen peroxide and 2-deoxy-D-glucose, a glycolysis inhibitor, in the porcine proximal kidney tubular cell line LLC-PK1, human hepatocyte cell line HepG2 cells, and HeLa cells [10–12].…”

“…We also elucidated that PEP drastically attenuates cellular injury induced by hydrogen peroxide and 2-deoxy-D-glucose, a glycolysis inhibitor, in the porcine proximal kidney tubular cell line LLC-PK1, human hepatocyte cell line HepG2 cells, and HeLa cells [10–12]. In addition, we demonstrated that PEP attenuates the elevation of aminotransferase leakage during organ preservation, histological changes, changes in oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content), and ATP content induced by 72 h of cold preservation of mouse liver in an ex vivo cold preservation system [11]. These in vitro and ex vivo results suggest that PEP is a functional carbohydrate metabolite with cytoprotective and antioxidative activities and may be suitable for organ cold preservation in a clinical transplantation setting.…”