The GC box/TIEG1-mediated repression of Bmal1 promoter
was additive to RORE-dependent repression by REV-ERB alpha, a well-known repressor of Bmal1 gene. In cell-based real-time assay, siRNA-mediated knock-down of TIEG1 caused period shortening of cellular bioluminescence rhythms driven by Bmal1-luciferase and Per2-luciferase reporters. These findings highlight an active role of TIEG1 in the normal clock oscillation and GC box-mediated regulation of Bmal1 transcription.”
“Neurohormesis refers to selleck a response to a moderate level of stress that enhances the ability of the nervous systems to resist more severe stress that might be lethal or cause dysfunction or disease. Neurohormetic phytochemicals, such as, resveratrol, sulforaphane, curcumin, and catechins, protect neurons against injury and disease. Naphthoquinones, such as, juglone and plumbagin, induce robust hormetic stress responses. However, the possibility that subtoxic dose of 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin) may protect against brain diseases ubiquitin-Proteasome pathway via the activation of an adaptive stress response pathway in the brain has not been investigated. In this study, we
examined the neurohormetic effect of a subtoxic dose of naphthazarin in a Parkinson’s disease model. It was found that, under these conditions, Smad inhibitor naphthazarin enhanced movement ability, prevented loss of dopaminergic neurons, and attenuated neuroinflammation in a 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson’s disease model. Furthermore, it was found that the neuroprotective effect of naphthazarin was mediated by the suppression of astroglial activation in response to 1-methyl-4-phenylpyridine treatment. In conclusion, we suggest that naphthazarin, in
view of its hormetic effect on neuroprotection, be viewed as a potential treatment for Parkinson’s disease and other neurodegenerative diseases associated with neuroinflammation. (c) 2012 Wiley Periodicals, Inc.”
“Polyunsaturated fatty acids (PUFA) of the n-3 series are essential for normal growth and development. The health effects of these fatty acids include reduction of cardiovascular risk due to antiarrhythmic, antiinflammatory, anti-thrombotic and lipid lowering actions. An increase in unsaturation of the muscle membrane fatty acids is associated with improved insulin sensitivity. Higher proportion of n-3 fatty acids may have beneficial roles, such as antiobesity effects and protection against the metabolic syndrome and type 2 diabetes mellitus through a number of metabolic effects. However, controversy exists on the different effects of n-6 and n-3 polyunsaturated fatty acids as well as on the interacting effect of dietary saturated and monounsaturated fat.