Effect of near-infrared light exposure on mitochondrial signaling in C2C12 muscle cells.

Near-infrared (NIR) light is a complementary therapy used to treat musculoskeletal injuries but the underlying mechanisms are unclear. Acute NIR light treatment (~800-950 nm; 22.8 J/cm(2)) induced a dose-dependent increase in mitochondrial signaling (AMPK, p38 MAPK) in differentiated muscle cells. Repeated NIR light exposure (4 days) appeared to elevate oxidative stress and increase the upstream mitochondrial regulatory proteins AMPK (3.1-fold), p38 (2.8-fold), PGC-1α (19.7%), Sirt1 (26.8%), and reduced RIP140 (23.2%), but downstream mitochondrial regulation/content (Tfam, NRF-1, Sirt3, cytochrome c, ETC subunits) was unaltered. Our data indicates that NIR light alters mitochondrial biogenesis signaling and may represent a mechanistic link to the clinical benefits.

Mitochondrial transcription factor A regulated ionizing radiation-induced mitochondrial biogenesis in human lung adenocarcinoma A549 cells.

Mitochondrial transcription factor A (TFAM), the first well-characterized transcription factor from vertebrate mitochondria, is closely related to mitochondrial DNA (mtDNA) maintenance and repair. Recent evidence has shown that the ratio of mtDNA to nuclearDNA (nDNA) is increased in both human cells and murine tissues after ionizing radiation (IR). However, the underlying mechanism has not as yet been clearly identified. In the present study, we demonstrated that in human lung adenocarcinoma A549 cells, expression of TFAM was upregulated, together with the increase of the relative mtDNA copy number and cytochrome c oxidase (COX) activity after α-particle irradiation. Furthermore, short hairpin RNA (shRNA)-mediated TFAM knockdown inhibited the enhancement of the relative mtDNA copy number and COX activity caused by α-particles. Taken together, our data suggested that TFAM plays a crucial role in regulating mtDNA amplification and mitochondrial biogenesis under IR conditions.

Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.

Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and phosphorylation levels of protein kinase A, protein kinase B, and CREB. Similarly, CREB inhibition reduced CREB activation and PGC-1α protein levels in selenoprotein H transfected cells. Moreover, selenoprotein H transfection increased the activity of mitochondrial complexes and prevented the ultraviolet B induced fall of mitochondrial membrane potential. We conclude that the effects of selenoprotein H on mitochondrial biogenesis and mitochondrial function are probably mediated through protein kinase A-CREB-PGC-1α and Akt/protein kinase B-CREB-PGC-1α pathways.

Effects of red light-emitting diode irradiation on dental pulp cells.

Light irradiation activates a range of cellular processes in a variety of cell types, including stem cells, and can promote tissue repair. This study investigated the effects of light-emitting diode (LED) exposure on dental pulp cells (DPCs). Dose response analysis at 20-second intervals up to 120 seconds demonstrated that a LED array emitting 653-nm red light stimulated significantly increased cell growth at 3 and 7 days post-irradiation with 40 (149 mJ/cm(2)) and 60 (224 mJ/cm(2)) seconds of radiant exposure. Double-dosing cells at days 1 and 4 of a 7-day culture period with 60-second (224 mJ/cm(2)) LED exposure significantly increased cell growth compared with a single dosing regime. BrdU analysis demonstrated significantly increased proliferation rates associated with significantly increased ATP, nitric oxide (NO), and mitochondrial metabolic activity. LED-stimulated NO levels were not reduced by inhibition of NO-synthase activity. Light exposure also rescued the inhibition of mitochondrial dysfunction and increased levels of in vitro mineralization compared with control. Media exchange experiments indicated that autocrine signaling was not likely responsible for red-light-induced DPC activity. In conclusion, data analysis indicated that 653-nm LED irradiation promoted DPC responses relevant to tissue repair, and this is likely mediated by increased mitochondrial activity.