Docherty 2016 Stem Cell Res Ther

From Bioblast
Publications in the MiPMap
Docherty CK, Salt IP, Mercer JR (2016) Lin28A induces energetic switching to glycolytic metabolism in human embryonic kidney cells. Stem Cell Res Ther 7:78.

Β» PMID: 27230676 Open Access

Docherty CK, Salt IP, Mercer JR (2016) Stem Cell Res Ther

Abstract: Loss of a cell's capacity to generate sufficient energy for cellular functions is a key hallmark of the ageing process and ultimately leads to a variety of important age-related pathologies such as cancer, Parkinson's disease and atherosclerosis. Regenerative medicine has sought to reverse these pathologies by reprogramming somatic cells to a more juvenile energetic state using a variety of stem cell factors. One of these factors, Lin28, is considered a candidate for modification in the reprogramming of cellular energetics to ameliorate the ageing process while retaining cell phenotype.

Over-expression of Lin28A resulted in key changes to cellular metabolism not observed in wild-type controls. Extracellular pH flux analysis indicated that Lin28A over expression significantly increased the rate of glycolysis, whilst high resolution oxygen respirometry demonstrated a reduced oxygen consumption. Western blot and real-time PCR analysis identified Hexokinase II as one of the key modulators of glycolysis in these cells which was further confirmed by increased glucose transport. A metabolic switching effect was further emphasised by Western blot analysis where the oxygen consuming mitochondrial complex IV was significantly reduced after Lin28A over expression.

Results from this study confirm that Lin28A expression promotes metabolic switching to a phenotype that relies predominantly on glycolysis as an energy source, while compromising oxidative phosphorylation. Mechanisms to augment regulated Lin28A in age related pathologies that are characterised by mitochondria dysfunction or in differentiated and aged post-mitotic cells is the future goal of this work. β€’ Keywords: Cellular metabolism, Glycolysis, Hexokinase II, Lin28, Reprogramming β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: UK Glasgow Mercer J

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Aging;senescence 

Organism: Human  Tissue;cell: Kidney, HEK  Preparation: Intact cells 

Coupling state: LEAK, ET  Pathway: ROX  HRR: Oxygraph-2k 

Labels, 2017-11 

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