TY - JOUR
T1 - Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation.
AU - Rainey-Smith, Stephanie
AU - Schroetke, Lars-Wilhelm
AU - Bahia, Parmvir
AU - Fahmi, Ahmed
AU - Skilton, Rachel
AU - Spencer, Jeremy P E
AU - Rice-Evans, Catherine
AU - Rattray, Marcus
AU - Williams, Robert J
PY - 2008/6/13
Y1 - 2008/6/13
N2 - Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300nM, 15min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression.
AB - Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300nM, 15min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression.
UR - http://www.scopus.com/inward/record.url?scp=43549110006&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1016/j.neulet.2008.04.056
U2 - 10.1016/j.neulet.2008.04.056
DO - 10.1016/j.neulet.2008.04.056
M3 - Article
SN - 0304-3940
VL - 438
SP - 29
EP - 33
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -