Maarman 2016 Abstract MitoFit Science Camp 2016

Melatonin rescues uric acid-induced impairment of respiration in myotubes.

Link:

Maarman G, Andrew BM, Blackhurst D, Ojuka EO (2016)

Event: MitoFit Science Camp 2016 Kuehtai AT

Hyperuricemia is associated with gout, hepatic steatosis and type 2 diabetes. It induces oxidative stress, lipogenesis and mitochondrial dysfunction in the liver [1-3]. However, the skeletal muscle is the greatest surface area exposed to hyperuricemia and yet no studies have investigated its effects on skeletal muscle.

To establish whether hyperuricemia modulates mitochondrial function, oxidative stress and triglyceride accumulation in myotubes and whether antioxidant treatment with melatonin can counteract these effects.

Differentiated C2C12 myotubes were exposed to uric acid (750µM, 72 hrs.) or uric acid + melatonin (10nM melatonin, 72 hrs). Mitochondrial function was assessed (high-resolution respirometry), spectrophotometry was used to assess oxidative damage to aconitase and triglyceride content. All values were compared to respective control groups (without uric acid and without melatonin).

Uric acid (1) reduced OXPHOS (60%) in the presence of pyruvate, glutamate and malate, (2) reduced aconitase activity by 37% and (3) increased triglyceride accumulation (52%) in C2C12 myotubes. Melatonin treatment restored OXPHOS (40%) and reduced triglyceride content (47%).

In conclusion, Hyperuricemia reduces complex-II respiration, induces damage to aconitase and triglyceride accumulation. Melatonin restored complex-II mediated mitochondrial function and normalized triglyceride accumulation. Melatonin could therefore be considered a therapy against hyperuricemia.

• O2k-Network Lab: ZA Cape Town Smith J, ZA Cape Town Ojuka EO

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Other  Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Skeletal muscle, Other cell lines 

Enzyme: Complex II;succinate dehydrogenase 

Coupling state: OXPHOS  Pathway: N  HRR: Oxygraph-2k  Event: D2  MitoFit Science Camp 2016 

Affiliations

1-Div Exercise Sc Sports Med (ESSM), Univ Cape Town, South Africa; 2-Div Chem Pathol, Dept Clinical Lab Sc, Fac Health Sc, Univ Cape Town, South Africa. - [email protected]

References

1. Villegas R, Xiang YB, Elasy T, Xu WH, Cai H, Cai Q, Linton MF, Fazio S, Zheng W, Shu XO (2012) Purine-rich foods, protein intake, and the prevalence of hyperuricemia: the Shanghai Men's Health Study. Nutr Metab Cardiovasc Dis 22:409-16.
2. Fam AG (2002) Gout, diet, and the insulin resistance syndrome. J Rheumatol 29:1350-5.
3. Choi HK (2010) A prescription for lifestyle change in patients with hyperuricemia and gout. Curr Opin Rheumatol 22:165-72.