Backbone dynamics of human parathyroid hormone (1-34): Flexibility of the central region under different environmental conditions

The presence of a stable tertiary structure in the bioactive N-terminal portion of parathyroid hormone (PTH), a major hormone in the maintenance of extracellular calcium homeostasis, is still debated. In this work, 15N relaxation parameters of the 33 backbone amides of human PTH(1\u201334) were determined in phosphate-buffered saline solution (PBS) and in the presence of dodecylphosphocholine (DPC) micelles. The relaxation parameters were analyzed using both the model-free formalism (G. Lipari and A. Szabo, Journal of the American Chemical Society, 1982, Vol. 104, pp. 4546\u20134549) and the reduced spectral density functions approach (J.-F. Lefevre, K. T. Dayie, J. W. Peng, and G. Wagner, Biochemistry, 1996, Vol. 35, pp. 2674\u20132686). In PBS, the region around Gly12 possesses a high degree of flexibility and the C-terminal helix is less flexible than the N-terminal one. In the presence of DPC micelles, the mobility of the entire molecule is reduced, but the stability of the N-terminal helix increases relative to the C-terminal one. A point of relatively higher mobility at residue Gly12 is still present and a new site of local mobility at residues 16\u201317 is generated. These results justify the lack of experimental nuclear Overhauser effect (NOE) restraints with lack of tertiary structure and support the hypothesis that, in the absence of the receptor, the relative spatial orientation of the two N- and C-terminal helices is undefined. The flexibility in the midregion of PTH(1\u201334), maintained in the presence of the membrane-mimetic environment, may enable the correct relative disposition of the two helices, favoring a productive interaction with the receptor

Investigation into the cancer protective effect of flaxseed in Tg.NK (MMTV/c-neu) mice, a murine mammary tumor model

The aim of the present study was to investigate whether low flaxseed doses relevant to human dietary exposure can prevent mammary tumors in transgenic Tg.NK mice, a model of breast cancer. Animals were exposed to flaxseed through the diet at human relevant levels. Tumor-related parameters and tumor development were evaluated. Hepatic cytochrome P450 and glutathione S-transferase activities were significantly reduced in animals receiving low flaxseed doses. An incidence of palpable tumors before sacrifice, a number of tumors per mouse, and a number of large tumors (>6 mm diameter) at necropsy were statistically significantly lower in the high flaxseed group compared to controls, suggesting a beneficial effect on tumor progression of small dietary doses of flaxseed. However, the number of tumor-bearing mice and multiplicity of tumors at necropsy were not statistically significantly lower compared to the controls. Thus, the effect of small dietary doses of flaxseed on mammary tumor development in Tg.NK mice remains to be established. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12263-011-0214-1) contains supplementary material, which is available to authorized users