Novel molecular triggers underlie valproate-induced liver injury and its alleviation by the omega-3 fatty acid DHA: role of inflammation and apoptosis.

Background/aim: Hepatic injury is a hallmark adverse reaction to Valproate (VPA), a common used drug in the management of numerous CNS disorders, including epilepsy. DHA has a myriad of health benefits, including renal- and hepato-protective effects. Unfortunately, however, the underpinnings of such liver-pertinent VPA- and DHA-actions remain largely undefined.

Valproate-induced liver injury: modulation by the omega-3 fatty acid DHA proposes a novel anticonvulsant regimen.

Background: The polyunsaturated, ω-3 fatty acid, docosahexaenoic acid (DHA), claims diverse cytoprotective potentials, although via largely undefined triggers. Thus, we currently first tested the ability of DHA to ameliorate valproate (VPA)-evoked hepatotoxicity, to modulate its anticonvulsant effects, then sought the cellular and molecular basis of such actions. Lastly, we also verified whether DHA may kinetically alter plasma levels/clearance rate of VPA.

Resveratrol reverses hydrogen peroxide-induced proliferative effects in human coronary smooth muscle cells: a novel signaling mechanism.

Background: In human coronary smooth muscle cells (HCSMCs), we tested the proatherogenic/proliferative potential of the reactive oxygen species (ROS), hydrogen peroxide (HP), and the ability of the polyphenol stilbene resveratrol (RSVL) to protect against such effects.

Methods: Activity for ERK1/2 and the kinase-G cascade were determined and correlated with HCSMC count before and after treatment with HP and/or RSVL.

Results: HP evoked concentration-dependent cell proliferation and stimulated ERK1/2 phosphorylation at active sites.

Progesterone inhibition of MDM2 p90 protein in MCF-7 human breast cancer cell line is dependent on p53 levels.

The mdm2 gene encodes several protein isoforms with different molecular weights (p90, p80, p76 and p57). MDM2 p90 (usually considered to be the major MDM2 protein) binds to and inactivates P53. We have recently shown that growth inhibition of MCF-7 human breast cancer cells by progesterone is associated with P53 down-regulation.

Differential recognition of resveratrol isomers by the human estrogen receptor-alpha: molecular dynamics evidence for stereoselective ligand binding.

Resveratrol (RSVL) is a phytoestrogen that occurs naturally in two forms (trans- (E) and cis- (Z)). We have conducted molecular dynamics (MD) studies to differentially characterize the estrogen receptor-alpha (ER-alpha) binding profiles of RSVL stereoisomers. Favorable orientations for RSVL isomers at the ER-alpha pocket were first inferred from (1) alignment with pharmacophoric elements of the pure ER-alpha agonists estradiol (E2) and (2) assessment of ligand recognition by the ER-alpha binding domain.

Resveratrol activates adenylyl-cyclase in human breast cancer cells: a novel, estrogen receptor-independent cytostatic mechanism.

Resveratrol (RSVL) is a well-established chemopreventive agent in human breast cancer models. The molecular basis of its action is far less characterized. We investigated the effects of RSVL on activity of adenylate- and guanylate-cyclase (AC, GC) enzymes; two known cytostatic cascades in MCF-7 breast cancer cells.

Recognition of resveratrol by the human estrogen receptor-alpha: a molecular modeling approach to understand its biological actions.

Objectives: Resveratrol (RSVL) is an edible phytoestrogen with multifaceted health benefits that may originate from binding to the estrogen receptors. Despite its structural similarity to the estrogen receptor-alpha (ER alpha) agonist diethylstilbestrol (DES), RSVL showed distinct biological profiles in estrogen-responsive biological systems. The molecular basis of such biological profiles has been undefined.

Resveratrol activates membrane-bound guanylyl cyclase in coronary arterial smooth muscle: a novel signaling mechanism in support of coronary protection.

Resveratrol (RSVL), an edible polyphenolic stilbene, claims a myriad of cardiovascular benefits. However, the molecular underpinnings of such actions are poorly understood. Currently, in sheep coronary arteries (SCA), RSVL markedly (threefold) enhanced cGMP formation (t(1/2): 6.

Endothelium-independent effect of estrogen on Ca(2+)-activated K(+) channels in human coronary artery smooth muscle cells.

Objective: Postmenopausal estrogen replacement therapy lowers the incidence of cardiovascular disease, suggesting that estrogens support cardiovascular function. Estrogens dilate coronary arteries; however, little is known about the molecular basis of how estrogen affects the human coronary circulation. The cellular/molecular effects of estrogen action on human coronary smooth muscle were investigated in the present study.