Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling
Abstract
There is accumulating evidence indicating that the growth inhibitory effect of dichloroacetate (DCA) on pulmonary arterial smooth muscle cells (PASMCs) may be associated with the reversal of the Warburg effect and initiation of the mitochondria‑dependent apoptotic pathway. Previous studies indicated that platelet‑derived growth factor (PDGF) promoted the Warburg effect and resulted in apoptotic resistance of PASMCs, which was attributed to activation of the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) signalling pathway. However, the mechanism underlying the pro‑apoptotic effect of DCA on PDGF‑treated PASMCs has not been thoroughly elucidated, and the effect of the Akt/glycogen synthase kinase‑3β (GSK‑3β) pathway inhibition concomitant with the effect of DCA on PASMC proliferation remains unclear. The growth of human PASMCs and the lactate concentration in extracellular medium of PASMCs were detected by Cell Counting Kit‑8 assays and a Lactate Colorimetric Assay kit, respectively. Cell apoptosis was evaluated by fluorescence activated cell sorting. The mitochondrial membrane potential (ΔΨm) was assessed with 5,5',6,6'‑tetrachloro‑1,1',3,3'‑tetraethylbenzimidazol‑carbocyanine iodide assays. The expression levels o...Continue Reading
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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis
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