Up-regulation of aldose reductase expression mediated by phosphatidylinositol 3-kinase/Akt and Nrf2 is involved in the protective effect of curcumin against oxidative damage Export

@article{citeulike:3681447, abstract = {Up-regulation of aldose reductase (AR) by reactive oxygen species (ROS) and aldehyde derivatives has been observed in vascular smooth muscle cells. However, the pathophysiological consequences of the induction of AR in vascular tissues are not fully elucidated. Herein we report that an herb-derived polyphenolic compound, curcumin, elicited a dose- and time-dependent increase in AR expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) significantly suppressed the curcumin-augmented mRNA levels and promoter activity of the AR gene. Luciferase reporter assays indicated that an osmotic response element in the promoter was essential for the responsiveness to curcumin. Curcumin accelerated the nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2), and overexpression of Nrf2, but not the dominant negative Nrf2, enhanced the promoter activity of the AR gene. Cells preincubated with curcumin demonstrated resistance to ROS-induced apoptotic death. These effects were significantly attenuated in the presence of AR inhibitors or small interfering RNAs, indicating a protective role for AR against ROS-induced cell damage. Taken together, the activation of PI3K and p38 MAPK by curcumin augmented the expression of the AR gene via Nrf2, and increased AR activity may be an important cellular response against oxidative stress.}, author = {Kang, Eun S. and Woo, Im S. and Kim, Hyo J. and Eun, So Y. and Paek, Kyung S. and Kim, Hye J. and Chang, Ki C. and Lee, Jae H. and Lee, Hoon T. and Kim, Jin-Hoi}, citeulike-article-id = {3681447}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.freeradbiomed.2007.05.006}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S089158490700322X}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17640564}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17640564}, day = {15}, doi = {10.1016/j.freeradbiomed.2007.05.006}, issn = {08915849}, journal = {Free Radical Biology and Medicine}, keywords = {aldose\_reductase, curcumin, nrf2, oxidative\_damage, pi3kakt}, month = {August}, number = {4}, pages = {535--545}, posted-at = {2008-11-24 17:54:58}, priority = {3}, title = {Up-regulation of aldose reductase expression mediated by phosphatidylinositol 3-kinase/Akt and Nrf2 is involved in the protective effect of curcumin against oxidative damage}, url = {http://dx.doi.org/10.1016/j.freeradbiomed.2007.05.006}, volume = {43}, year = {2007} }

TY - JOUR ID - citeulike:3681447 L3 - citeulike-article-id:3681447 N2 - Up-regulation of aldose reductase (AR) by reactive oxygen species (ROS) and aldehyde derivatives has been observed in vascular smooth muscle cells. However, the pathophysiological consequences of the induction of AR in vascular tissues are not fully elucidated. Herein we report that an herb-derived polyphenolic compound, curcumin, elicited a dose- and time-dependent increase in AR expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) significantly suppressed the curcumin-augmented mRNA levels and promoter activity of the AR gene. Luciferase reporter assays indicated that an osmotic response element in the promoter was essential for the responsiveness to curcumin. Curcumin accelerated the nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2), and overexpression of Nrf2, but not the dominant negative Nrf2, enhanced the promoter activity of the AR gene. Cells preincubated with curcumin demonstrated resistance to ROS-induced apoptotic death. These effects were significantly attenuated in the presence of AR inhibitors or small interfering RNAs, indicating a protective role for AR against ROS-induced cell damage. Taken together, the activation of PI3K and p38 MAPK by curcumin augmented the expression of the AR gene via Nrf2, and increased AR activity may be an important cellular response against oxidative stress. IS - 4 JF - Free Radical Biology and Medicine SN - 08915849 EP - 545 TI - Up-regulation of aldose reductase expression mediated by phosphatidylinositol 3-kinase/Akt and Nrf2 is involved in the protective effect of curcumin against oxidative damage VL - 43 SP - 535 KW - aldose_reductase KW - curcumin KW - nrf2 KW - oxidative_damage KW - pi3kakt AU - Kang, Eun AU - Woo, Im AU - Kim, Hyo AU - Eun, So AU - Paek, Kyung AU - Kim, Hye AU - Chang, Ki AU - Lee, Jae AU - Lee, Hoon AU - Kim, Jin-Hoi PY - 2007/08/15/ UR - http://dx.doi.org/10.1016/j.freeradbiomed.2007.05.006 ER -