Houghton 2014 Abstract MiP2014

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The effect of bioactive phenolics on chronic mitochondrial stress associated with the onset of diabetes.
Link:
Houghton M
Mitochondr Physiol Network 19.13 - MiP2014

Houghton M, Boyle JP, Tumova S, Kerimi A, Williamson G (2014)

Event: MiP2014

There is sufficient evidence to suggest that mitochondrial (mt) dysfunction plays a pivotal role in the onset of type II diabetes mellitus and that dietary (poly)phenols may help alleviate this [1-4]. Colonic microbial metabolites of (poly)phenols are of particular interest, as they can be present in blood in vivo at high concentration in peripheral tissues [5]. Furthermore, cells are chronically exposed to these compounds for long periods of time which implies that they could have a lasting effect on mt function.

To study these potential effects, human hepatocyte cells were cultured in high glucose in the presence of (poly)phenols and relevant biomarkers investigated. Mitochondria were isolated and characterized. Spectrophotometric enzymic assays were used to assess the activity of the protein complexes of the electron transfer-pathway (ET-pathway), and reactive oxygen species (ROS) generation was studied using a fluorescence assay. In addition, high-resolution respirometry on corresponding intact cells enabled the measurement of mt respiration and analysis of oxidative phosphorylation. We find that high glucose concentration significantly decreases mt ET-pathway Complex I NADH oxidase activity (Fig. 1), and the ability of biologically active molecules to affect this modulation will be presented.


O2k-Network Lab: UK Leeds Peers C


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes  Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Liver  Preparation: Isolated mitochondria  Enzyme: Complex I 


HRR: Oxygraph-2k, O2k-Spectrophotometer  Event: B2, Oral  MiP2014 

Affiliation

University Leeds, United Kingdom. – fsmjh@leeds.ac.uk

Figure 1

MiP2014 Houghton Figure.jpg
Figure 1: Electron transfer Complex I NADH oxidase (CI) activity in mitochondria isolated from human HepG2 cells, maintained in MEM Eagle supplemented with 10% FBS, in the presence of 5.5 or 25 mM glucose, for 24 h. Mt preparations were assayed in 150 μM NADH and absorbance at 340 nm monitored for 1 h. Enzyme activity (U) is equivalent to μmol NADH oxidised min-1∙mg-1 total protein. Bars represent mean+SD; N=3 (*P<0.05).

References and acknowledgements

Supported by European Research Council Advanced Grant POLYTRUE? (322467).

  1. Yang H, Jin X, Kei Lam CW, Yan SK (2011) Oxidative stress and diabetes mellitus. Clin Chem Lab Med 49: 1773-82.
  2. Williamson G (2013) Possible effects of dietary polyphenols on sugar absorption and digestion. Mol Nutr Food Res 57: 48-57.
  3. Bahadoran Z, Mirmiran P, Azizi F (2013) Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. J Diabetes Metab Disord 12: 43.
  4. Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A (2009) Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol 297: 1876-81.
  5. Williamson G, MN Clifford (2010) Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr 104 Suppl 3: 48-66.