Curcumin treatment enhances the effect of exercise on mitochondrial biogenesis in skeletal muscle by increasing cAMP levels.

BACKGROUND: In response to physiologic stressors, skeletal muscle has the potential to elicit wide variety of adaptive responses, such as biogenesis of mitochondria and clearance of damaged mitochondria to promote healthy muscle. The polyphenol curcumin, derived from the rhizome Curcuma longa L., is a natural antioxidant that exhibits various pharmacological activities and therapeutic properties. However, the effect of curcumin on the regulation of mitochondrial biogenesis in skeletal muscle remains unknown. The present study aimed to examine the effects of combination of endurance training (eTR) and curcumin treatment on the expression of AMPK, SIRT1, PGC-1α, and OXPHOS subunits, mitochondrial DNA copy number, and CS activity in rat skeletal muscle. Furthermore, the present study also examined the effect of exercise and curcumin treatment on the levels of cAMP and downstream targets of PKA including phosphorylated CREB and LKB-1. METHODS: Ten-week-old male Wistar rats were randomly divided into non-eTR and eTR groups. Low doses (50 mg/kg-BW/day) or high doses (100 mg/kg-BW/day) of curcumin dissolved in dimethyl sulfoxide (DMSO) were injected intraperitoneally in all animals for 28 days to investigate the effect of curcumin alone and the combined effect of curcumin with eTR. Western blotting (WB) and immunoprecipitation (IP) were performed to detect the presence of proteins. RESULTS: Our results demonstrated that combination of curcumin treatment and eTR increased the expression of COX-IV, OXPHOS subunits, mitochondrial DNA copy number and CS activity in the gastrocnemius (Gas) and soleus (Sol) muscles. In addition, this combination increased AMPK phosphorylation, NAD(+)/NADH ratio, SIRT1 expression, and PGC-1α deacetylation. Furthermore, curcumin treatment as well as exercise also increased levels of cAMP and downstream target of PKA including phosphorylation CREB and LKB-1 which are involved in the regulation of mitochondrial biogenesis. CONCLUSION: Taken together, these results suggest that the combination of curcumin treatment and eTR has the potential to accelerate mitochondrial biogenesis in skeletal muscle by increasing cAMP levels.

Influence of long-distance seed dispersal on the genetic diversity of seed rain in fragmented Pinus densiflora populations relative to pollen-mediated gene flow.

Long-distance dispersal (LDD) of seeds has a critical impact on species survival in patchy landscapes. However, relative to pollen dispersal, empirical data on how seed LDD affects genetic diversity in fragmented populations have been poorly reported. Thus, we attempted to indirectly evaluate the influence of seed LDD by estimating maternal and paternal inbreeding in the seed rain of fragmented 8 Pinus densiflora populations. In total, the sample size was 458 seeds and 306 adult trees. Inbreeding was estimated by common parentage analysis to evaluate gene flow within populations and by sibship reconstruction analysis to estimate gene flow within and among populations. In the parentage analysis, the observed probability that sampled seeds had the same parents within populations was significantly larger than the expected probability in many populations. This result suggested that gene dispersal was limited to within populations. In the sibship reconstruction, many donors both within and among populations appeared to contribute to sampled seeds. Significant differences in sibling ratios were not detected between paternity and maternity. These results suggested that seed-mediated gene flow and pollen-mediated gene flow from outside population contributed some extent to high genetic diversity of the seed rain (H E > 0.854). We emphasize that pine seeds may have excellent potential for gene exchange within and among populations.

Gene-nutrient and gene-gene interactions of controlled folate intake by Japanese women.

Elevated serum total homocysteine (tHcy) levels are associated with increased risk for cardiovascular disease and dementia. The prevalence rates of homozygous mutants among Japanese women (n = 300) were 17.3%, 1.3%, 18.6%, and 5.3% for methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC-1) A80G, and methionine synthase (MS) A2756G, respectively. The tHcy value was significantly lower (p < 0.001) in young women with CC or CT of MTHFR than with TT (10.9+/-4.7 micromol/L) (n =250). Diversities of serum folate and tHcy in women with 23 combinations of different alleles at low folate intake converged to the highest (34.0+/-8.6 nmol/L) and lowest (7.6+/-1.5 micromol/L) levels, respectively, after folic acid (400 microg/day) supplementation. In the regression equation ( y= ax + b) of serum folate ( y nmol/L) plotted against mean folate intake ( x microg/day), the values of "a" were 0.032, 0.037, and 0.045 for individuals with CC, CT, and TT alleles, respectively, of MTHFR.