Creatine Supplementation Normalizes Mutagenesis of Mitochondrial DNA as Well as Functional Consequences

Abstract

Mutations of mitochondrial (mt) DNA play a role in neurodegeneration, normal aging, premature aging of the skin (photoaging), and tumors. We and others could demonstrate that mtDNA mutations can be induced in skin cells in vitro and in normal human skin in vivo by repetitive, sublethal ultraviolet (UV)-A-irradiation. These mutations are mediated by singlet oxygen and persist in human skin as long-term biomarkers of UV exposure. Although mtDNA exclusively encodes for the respiratory chain, involvement of the energy metabolism in mtDNA mutagenesis and a protective role of the energy precursor creatine have thus far not been shown. We assessed the amount of a marker mutation of mtDNA, the so-called common deletion, by real-time PCR. Induction of the common deletion was paralleled by a measurable decrease of oxygen consumption, mitochondrial membrane potential, and ATP content, as well as an increase of matrix metalloproteinase-1. Mitochondrial mutagenesis as well as functional consequences could be normalized by increasing intracellular creatine levels. These data indicate that increase of the energy precursor creatine protects from functionally relevant, aging-associated mutations of mitochondrial DNA.

Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

“…Sharov et al 26 showed that exogenous phosphocreatine administration attenuated ischemic damage and reduced necrotic zone with maintenance of membrane integrity. Berneburg et al 27 reported that there was a link between mitochondrial DNA mutations and cellular energy metabolism. In addition, authors showed that mitochondrial mutagenesis could be normalized by creatine supplementation.…”

Dissecting the Impact of Chemotherapy on the Human Hair Follicle

“…HFs were homogenized, and genomic DNA was isolated by the Wizard SV genomic DNA purification system (Promega, Mannheim, Germany) following the manufacturer's instructions. Detection of the common deletion was performed as described previously 38,61 and levels of the common deletion and undeleted mitochondrial DNA sequences were detected with real-time PCR. The normalized level of common deletion in vehicle-treated follicles (ϭ1) was compared with the normalized common deletion level of 4-HC-treated follicles.…”

Effect of free creatine therapy on cisplatin-induced renal damage

“…23 In addition, antiinflammatory activities of creatine on endothelial cells have been shown recently. 4 Berneburg et al 5 observed that creatine supplementation normalized ultraviolet-A-irradiation induced mitochondrial mutagenesis and showed the link between mtDNA common deletion rate and energy Notes: Values are expressed as mean ± Standard deviation * median (minimum-maximum). When groups were evaluated in terms of progress, no significant difference was found in all three groups (p ¼ 0.959, 0.594, and 0.173, respectively).…”

“…Creatine has been reported to have antiinflammatory, antioxidant effects and it has been shown that it acts as a free radical scavenger. [4][5][6][7][8] Besides this, recent reports supported that Cr has additional beneficial effects on various neurological, muscular, cardiovascular disorders, and aging. [9][10][11][12][13][14] The aim of this study is to investigate the possible protective effect of creatine therapy on cisplatin-induced nephrotoxicity.…”