Widlund 2014 Abstract MiP2014
|Resveratrol as a double edged sword on mitochondrial function.|
Resveratrol (Resv), a polyphenolic compound, impacts the function of isolated mitochondria, but its modulation of mitochondria in whole cells remains poorly defined. In experiments with isolated mitochondria, Resv inhibits the activity of several complexes in the electron transfer-pathway (ET-pathway) [1,2]. In experiments during which animals were exposed to Resv, an increase in mitochondrial activity by Resv was observed [3,4]. Therefore, the aim of the present study was to study the effect of Resv on the mitochondrial activity in HeLa cells, noninvasively.
A Beckman Coulter Z2 Cell and Particle Counter as well as an ICELLigence system were used to analyze cell number, proliferation and size. Fluorescence-activated cell sorting FACS was used to characterize each cell in regard to relative ﬂuorescence intensity. A Seahorse XF-24 analyzer was used to test effects of Resv on mitochondrial activity. Quantitative PCR was used to determine relative amounts of a known sequence of key genes related to mitochondrial function.
Our results show that Resv decreases the cell number dose-dependently in both HeLa WT and HeLa Rho 0 (depleted of mtDNA), but show no effect on cell proliferation with regard to functional mitochondria. A significant increase in cell diameter was observed in HeLa WT but not in HeL Rho 0; hence functional mitochondria seem to be a prerequisite for the cell enlargement effect by Resv. An overall increase in mitochondrial number, membrane potential and reactive oxygen species was observed in HeLa Rho 0 compared to HeLa WT. Exposure to Resv induced only small (statistically insignificant) differences. The oxygen consumption rate was dose-dependently up-regulated by Resv, which also is observed on extracellular acidification rate. To further evaluate if mitochondria of HeLa WT and HeLa Rho 0 cells were affected by Resv treatment, the expression levels of several key genes related to mitochondrial function were measured, leading to results consistent with previous reports .
Our results indicate that in HeLa cells Resv upregulates mitochondrial respiration and cellular glycolysis.
Labels: MiParea: Respiration, Pharmacology;toxicology
Tissue;cell: HeLa Preparation: Intact cells
Regulation: Aerobic glycolysis Coupling state: ROUTINE
Event: B4, Oral MiP2014: Resveratrol
Dep Sc, Systems Models, Roskilde Univ, Denmark. – [email protected]
References and acknowledgements
Supported in part by the Danish Council for Strategic Research.
- Zini R, Morin C, Bertelli A, Bertelli AA, Tillement JP (1999) Effects of resveratrol on the rat brain respiratory chain. Drugs Exp Clin Res 25: 87-97.
- Zheng J, Ramirez VD (2000) Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals. Br J Pharmacol 130: 1115-23.
- Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127: 1109-22.
- Csiszar A, Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson K, de Cabo R, Pacher P, Zhang C, Ungvari Z (2009) Resveratrol induces mitochondrial biogenesis in endothelial cells. Physiol Heart Circ Physiol 297: 13-20.
- Baur J (2010) Biochemical effects of SIRT1 activators. Biochim Biophys Acta 1804: 1626-34.