For this reason, it was thought until recently that most biological effects of retinol were exclusively dependent on its cellular conversion to retinoic acid. Nonetheless, there has been a growing body of evidence in the last two decades that retinol per se may exert important biological effects, especially through mechanisms that involve modulation of redox states and cell signaling ( Acin-Perez et al., 2010 and Gelain et al., 2006). Here, we observed that Akt PF-562271 molecular weight and p38 phosphorylation took place within 60 min of retinol incubation,

with phosphorylation peaks in the range of 15–30 min. This rapid effect is not compatible to a genomic action that would be dependent on gene transcription activation by RAR/RXR, but is more similar to the more recent nongenomic mechanism of action exerted by retinoids widely reported CHIR-99021 nmr for different authors ( Canon et al., 2004, Liou et al., 2005 and Masia et al., 2007). It is noteworthy that Akt

and p38 were observed, in different cell models, to be implicated in the process of malignant cell transformation (Castaneda et al., 2010 and Han and Sun, 2007). In previous works, we observed that retinol activated cell proliferation, induced proliferative focus formation and enhanced MMP-2 activity in Sertoli cells (Dal-Pizzol et al., 2001b, Dalmolin et al., 2007, Gelain et al., 2006 and Klamt et al., 2003b). Recently, we also observed that p38 inhibition reverses many of these effects, suggesting that p38 activation may be involved in process of induction of transformation caused by pro-oxidant concentrations of retinol (unpublished data, manuscript in preparation). Also recently, oxidative stress-induced RAGE

up-regulation was reported to be important for the survival response of cancer cells to oxidant injury, contributing for the increased resistance of transformed cells against apoptosis caused by oxidative damage (Kang et al., 2010). It is possible that RAGE up-regulation we observed in Sertoli cells may constitute an adaptive response to the pro-oxidant conditions set by retinol, which would Phosphoglycerate kinase be important for cell survival during transformation processes triggered by common pathways controlled by cell cycle-related protein kinases such as Akt and p38. We have no competing interests. This work was financed by the Brazilian agencies CNPq (IBN-Net #01.06.0842-00 and 470234/2008), FAPERGS (PqG 06/2010) and PROPESQ-UFRGS. “
“Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane), an orange-yellow component of turmeric (also known as Indian saffron, turmeric yellow or curry powder), is a natural polyphenol product isolated from the Curcuma longa plant rhizome.