Structure-activity relationship of resveratrol and its analogue, 4,4'-dihydroxy-trans-stilbene, toward the endothelin axis in human endothelial cells.

Resveratrol inhibits endothelin-1, a vascular tension regulator. We synthesized the resveratrol analogue 4,4'-dihydroxy-trans-stilbene with 2 hydroxyl groups in the 4 and 4' position to obtain a molecule more active than resveratrol (3,4',5-trihydroxy-trans-stilbene). The results demonstrate that 4,4'-dihydroxy-trans-stilbene led to a significant decrease in total endothelin-1 secretion and in endothelin-1 messenger RNA (mRNA) levels in human endothelial cells.

An improved phenylarsine oxide-affinity method identifies triose phosphate isomerase as a candidate redox receptor protein.

Reversible oxidation on proteins of vicinal thiols to form intraprotein disulfides is believed to be an important means by which redox sensitivity is conferred on cellular signaling and metabolism. Affinity chromatography using immobilized phenylarsine oxide (PAO), which binds preferentially to vicinal thiols over monothiols, has been used in very limited studies to isolate the fraction of cellular proteins that exhibit reversible oxidation of vicinal thiols to presumed disulfide bonds. A challenge to the use of PAO-affinity chromatography for isolation of readily oxidizable vicinal thiol proteins (VTPs) has been the lack of a disulfide reducing agent that reverses oxidation of the PAO-binding protein thiols and maintains these in the reduced state necessary to bind PAO but does not also compete with the VTPs for binding to the immobilized PAO.

The resveratrol analogue 4,4'-dihydroxy-trans-stilbene inhibits cell proliferation with higher efficiency but different mechanism from resveratrol.

Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and wine, which shows antiproliferative activity. We previously found that 4-hydroxy group in the trans conformation was absolutely required for the inhibition of cell proliferation. In the present work we have synthesized the resveratrol analogue 4,4'-dihydroxy-trans-stilbene, which contains two OH in 4' and 4 positions, with the aim of developing a compound with an antiproliferative potential higher than that of resveratrol, on the basis of the correlation between structure and activity previously observed.

Degradation of p21CDKN1A after DNA damage is independent of type of lesion, and is not required for DNA repair.

The inhibitor of cyclin-dependent kinases p21CDKN1A plays a fundamental role in several pathways involved in the DNA damage response, like checkpoint-mediated cell cycle arrest, transcription, apoptosis, and DNA repair. Although p21 protein level is regulated by proteasomal degradation, the relationship of this process with DNA repair pathways is not yet clear. In addition, the role of protein/protein interaction in regulating turnover of p21 protein, is controversial.

Loss of histone H2AX increases sensitivity of immortalized mouse fibroblasts to the topoisomerase II inhibitor etoposide.

In mammalian cells, the H2AX histone is rapidly phosphorylated upon the induction of DNA double strand breaks and promotes their repair, which is required for preserving genomic integrity. Etoposide is an inhibitor of DNA topoisomerase II, which causes DNA breaks and induces H2AX phosphorylation. To elucidate whether H2AX may affect cellular sensitivity to etoposide, we studied the response to this agent in immortalized embryonic fibroblasts derived from H2AX knockout mice.