Stem cells and neuroprotection: understanding the players.

The use of neuroprotective therapies begs the question of how such therapies could affect preexisting stem cell populations within the host, as well as those introduced through cell-replacement therapy. Multiple mechanisms may mediate stem cell responses to neuroprotectants such as host/donor age and gender, cellular lineage/differentiation status, and mitochondrial dynamics. Current therapeutic sources for stem cells are embryonic, somatic, or induced pluripotent, with very little known about the effects of gender, age, cell type, and mitochondrial dynamics.

Role of lipid peroxidation in cellular responses to D,L-sulforaphane, a promising cancer chemopreventive agent.

D,L-sulforaphane (SFN), a synthetic analogue of the broccoli-derived l-isomer, is a highly promising cancer chemopreventive agent substantiated by inhibition of chemically induced cancer in rodents and prevention of cancer development and distant site metastasis in transgenic mouse models of cancer. SFN is also known to inhibit growth of human cancer cells in association with cell cycle arrest and reactive oxygen species-dependent apoptosis, but the mechanism of these cellular responses to SFN exposure is not fully understood. Because 4-hydroxynonenal (4-HNE), a product of lipid peroxidation (LPO), the formation of which is regulated by hGSTA1-1, assumes a pivotal role in oxidative stress-induced signal transduction, we investigated its contribution in growth arrest and apoptosis induction by SFN using HL60 and K562 human leukemic cell lines as a model.

4-Hydroxynonenal induces p53-mediated apoptosis in retinal pigment epithelial cells.

4-Hydroxynonenal (4-HNE) has been suggested to be involved in stress-induced signaling for apoptosis. In present studies, we have examined the effects of 4-HNE on the intrinsic apoptotic pathway associated with p53 in human retinal pigment epithelial (RPE and ARPE-19) cells. Our results show that 4-HNE causes induction, phosphorylation, and nuclear accumulation of p53 which is accompanied with down regulation of MDM2, activation of the pro-apoptotic p53 target genes viz.

Estrogen actions on mitochondria--physiological and pathological implications.

Estrogens are potent neuroprotective hormones and mitochondria are the site of cellular life-death decisions. As such, it is not surprising that we and others have shown that estrogens have remarkable effects on mitochondrial function. Herein we provide evidence for a primary effect of estrogens on mitochondrial function, achieved in part by the import of estrogen receptor beta (ERbeta) into the mitochondria where it mediates a number of estrogen actions on this vital organelle.

Characterization of growth and differentiation in a telomerase-immortalized human corneal epithelial cell line.

Purpose: To develop and characterize a telomerase-immortalized human corneal epithelial cell line (hTCEpi) to serve as an in vitro model for studying the molecular mechanisms involved in regulating human corneal epithelial cell differentiation.

Methods: Primary cultures of human corneal epithelial cells were infected with a retroviral vector encoding human telomerase reverse transcriptase (hTERT). Infected hTCEpi cells were selected, cloned, and characterized to identify telomerase activity, proliferative capacity, karyotype, and differentiative potential in routine culture and under consecutive submerged and air-lifted conditions.

4-ethoxymethylphenol: a novel phytoestrogen that acts as an agonist for human estrogen receptors.

Estrogen is the natural agonist of the estrogen receptor (ER). However, certain plant-derived compounds or phytoestrogens have been identified that mimic estrogens and act as agonists and/or antagonists of ERs, depending on subtype and target tissue. Using thin layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS), and proton nuclear magnetic resonance (1H-NMR), we identified a simple phenol, 4-ethoxymethylphenol (4EM), found in Maclura pomifera that acts as an agonist of ER-alpha and ER-beta in HeLa and MCF-7 cells.

A peroxisome proliferator-activated receptor-gamma agonist and the p53 rescue drug CP-31398 inhibit the spontaneous immortalization of breast epithelial cells.

Cell immortalization is a critical and rate-limiting step in cancer progression. Agents that inhibit cell immortalization may have utility for novel molecular chemopreventive strategies. Preimmortal breast epithelial cells derived from a patient with the Li-Fraumeni Syndrome (LFS) can spontaneously immortalize in vitro at a measurable and reproducible frequency.