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Title: Metabolic parameters involved in Keloid Scar formation
Keywords: keloid fibroblasts, cancer, hexokinase II, pyruvate dehydrogenase, glycolysis, bioenergetics
Issue Date: 29-Jan-2009
Citation: ANNETTE SHOBA VINCENT (2009-01-29). Metabolic parameters involved in Keloid Scar formation. ScholarBank@NUS Repository.
Abstract: Cultured human skin keloid fibroblasts (KF) showed bioenergetics similar to cancer cells in generating ATP mainly from glycolysis as demonstrated by increased lactate production and rate of glucose utilization. The basal oxygen consumption was lower in KF possibly due to their switch to aerobic glycolysis from mitochondrial oxidative phosphorylation (OXPHOS). However, when fortified with excess exogenous respiratory substrates, ATP production and mitochondrial membrane potential increased to a similar maximal level compared to normal fibroblasts (NF). Although KF exhibit the Warburg phenomenon of aerobic glycolysis, these benign tumor cells retain ability to oxidize pyruvate unlike malignant cells. The overactive system observed in KF was attributed to their glycolytic/hexokinase phenotype. The distribution of mitochondrial-bound hexokinase (HKII) and cytosolic HK was near equal in NF but HKII activity was significantly higher in KF, explaining the greater inhibition by 3-bromopyruvate (3-BP), a specific inhibitor of HKII. Likewise, mRNA and protein levels of HKII were elevated. The mitochondrial localization of HKII in KF involved the Akt pathway. HKII represented an ideal therapeutic target. Treatment with 3-BP reduced cell viability and depleted intracellular ATP levels more significantly than NF. Targeting the altered bioenergetic phenotype of KF reduced migration and extracellular matrix secretion reaffirming the potential of 3-BP as therapy.
Appears in Collections:Ph.D Theses (Open)

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