Publications (3)9.36 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D) inhibits the growth of prostate epithelial cells, however the underlying mechanisms have not been clearly delineated. In the current study, the impact of 1,25(OH)(2)D on the rapid activation of extracellular-regulated kinase (ERK) 1/2 and protein kinase C alpha (PKC alpha), and the role of these pathways in growth inhibition was examined in immortalized mouse prostate epithelial cells, MPEC3, that exhibit stem/progenitor cell characteristics. 1,25(OH)(2)D treatment suppressed the growth of MPEC3 in a dose and time dependent manner (e.g., 21% reduction at three days with 100 nM 1,25(OH)(2)D treatment). However, ERK1/2 activity was not altered by 100 nM 1,25(OH)(2)D treatment for time points from 1 min to 1 h in either serum-containing or serum-free medium. Similarly, PKC alpha activation (translocation onto the plasma membrane) was not regulated by short-term treatment of 100 nM 1,25(OH)(2)D. In conclusion, 1,25(OH)(2)D did not mediate rapid activation of ERK1/2 or PKC alpha in MPEC3 and therefore the growth inhibitory effect of 1,25(OH)(2)D is independent of rapid activation of these signaling pathways in this cell type.
- [Show abstract] [Hide abstract] ABSTRACT: The aim of the current study was to determine the effects and the mechanisms of inclusion of dietary whey protein, high calcium, and high vitamin D intake with either a high-sucrose or high-fat base diets on body composition of rodents. Male Wistar rats were assigned to either no whey protein, suboptimal calcium (0.25%), and vitamin D (400 IU/kg) diet (LD), or a diet containing whey protein, high calcium (1.5%), and vitamin D (10 000 IU/kg) diet (HD), and either high-fat (40% of energy) or high-sucrose (60%) base diets for 13 weeks. Liver tissue homogenates were used to determine [(14)C]glucose and [(14)C]palmitate oxidation. mRNA expression of enzymes related to energy metabolism in liver, adipose, and muscle, as well as regulators of muscle mass and insulin receptor was assessed. The results demonstrated that there was reduced accumulation of body fat mass (P = .01) and greater lean mass (P = .03) for the HD- compared to LD-fed group regardless of the background diet. There were no consistent differences between the LD and HD groups across background diets in substrate oxidation and mRNA expression for enzymes measured that regulate energy metabolism, myostatin, or muscle vascular endothelial growth factor. However, there was an increase in insulin receptor mRNA expression in muscle in the HD compared to the LD groups. In conclusion, elevated whey protein, calcium, and vitamin D intake resulted in reduced accumulation of body fat mass and increased lean mass, with a commensurate increase in insulin receptor expression, regardless of the level of calories from fat or sucrose.
- [Show abstract] [Hide abstract] ABSTRACT: High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1alpha,25-dihydroxyvitamin D hydroxylase (1alpha-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D) from the substrate 25-hydroxyvitamin D (25OHD). Expression and dietary regulation of 1alpha-hydroxylase in tissues associated with energy metabolism, including adipose tissue, has not been assessed. Male Wistar rats were fed a high calcium (1.5%) and high vitamin D (10,000IU/kg) or a low calcium (0.25%), low vitamin D (400IU/kg) with either a high fat (40% energy) or high sucrose (66% energy) dietary background for 14 weeks. Expression of 1alpha-hydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1alpha-Hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 25OHD treatment at 10nM levels induced 1,25(OH)(2)D responsive gene, CYP24, and this response was reduced in the presence of the p450 inhibitor, ketoconazole. In addition, (3)H 25OHD was converted to (3)H 1,25(OH)(2)D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that 1alpha-hydroxylase is expressed in adipose tissue and is functional in cultured adipocytes. Thus, the capacity for local production may play a role in regulating adipocyte growth and metabolism.
Purdue UniversityWest Lafayette, Indiana, United States