GRIM-19 and p16(INK4a) synergistically regulate cell cycle progression and E2F1-responsive gene expression.

GRIM-19 (Gene associated with Retinoid-IFN-induced Mortality-19) was originally isolated as a growth suppressor in a genome-wide knockdown screen with antisense libraries. Like classical tumor suppressors, mutations, and/or loss of GRIM-19 expression occur in primary human tumors; and it is inactivated by viral gene products. Our search for potential GRIM-19-binding proteins, using mass spectrometry, that permit its antitumor actions led to the inhibitor of cyclin-dependent kinase 4, CDKN2A.

Identifying the changes in gene profiles regulating the amelioration of age-related oxidative damages in kidney tissue of rats by the intervention of adult-onset calorie restriction.

This study was initiated to investigate gene expression profiles that are involved in the molecular mechanisms regulating the amelioration of age-related oxidative damages in male Fischer-344 rats (12 months) through adult-onset calorie restriction (CR) intervention for 6 months. The adult-onset CR was initiated with 10 and 25% restriction for the first and second weeks, respectively, and then maintained at 40% throughout the experiment. The adult-onset CR significantly (p < 0.

Regulating the age-related oxidative damage, mitochondrial integrity, and antioxidative enzyme activity in Fischer 344 rats by supplementation of the antioxidant epigallocatechin-3-gallate.

In this study, epigallocatechin-3-gallate (EGCG) was examined for the first time for its anti-aging effect on middle-aged male Fischer 344 rats as a dietary supplement at 50 (low dose) and 500 (high dose) mg/kg/day over a 6-month period. Such levels of EGCG concentration were well-tolerated by rats without causing tissue damage or dysfunction in the liver and kidney, as evaluated by histopathological and biochemical observations. Compared to the rats in the low-dose and control groups, rats fed with high-dose EGCG showed a significant decline in the concentration of 8-hydroxy-2'-deoxyguanosine in the plasma while maintaining a better mitochondrial potential in the peripheral lymphocytes and preventing the deletion of ND4 region from mitochondrial DNA in the liver.

Effects of epigallocatechin-3-gallate on mitochondrial integrity and antioxidative enzyme activity in the aging process of human fibroblast.

Mitochondrial integrity and antioxidative enzyme activity are two of the determinants of intracellular reactive oxygen species (ROS) accumulation probably underlying the aging mechanism. In this study, epigallocatechin-3-gallate (EGCG) was examined for its antiaging effect on human diploid fibroblasts (HDF). EGCG was evaluated for its cytotoxicity, and LC50 values were 78.

Thapsigargin resistance in human prostate cancer cells.

Background: Thapsigargin (TG) is a potent inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+ ATPases (SERCAs). TG-based prodrugs are being developed for the treatment of prostate cancer (PC). To develop optimal TG-based therapeutics it is important to understand the mechanisms of resistance to TG that may potentially occur in cancer cells.

A Mediator-responsive form of metazoan RNA polymerase II.

RNA polymerase II (Pol II), whose 12 subunits are conserved across eukaryotes, is at the heart of the machinery responsible for transcription of mRNA. Although associated general transcription factors impart promoter specificity, responsiveness to gene- and tissue-selective activators additionally depends on the multiprotein Mediator coactivator complex. We have isolated from tissue extracts a distinct and abundant mammalian Pol II subpopulation that contains an additional tightly associated polypeptide, Gdown1.