Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1835664 (TOC)
 2,763 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemoprevention strategies for brain tumors (specifically gliomas) are few and surprisingly poorly investigated. We have studied the effects of tocopherols (TOCs; vitamin E) on proliferation and death processes of murine glioma C6 cells. These vitamers showed different cell uptake and concentration- and time-dependent inhibitory effects on cell growth that were significant at the lowest concentrations tested (1-10 microM). However, the inhibitory potency of TOCs seemed to reflect at least in part their actual cell concentrations at steady state, with the order of magnitude gamma-TOC >or= alpha-TOC > delta-TOC approximately or = beta-TOC. Moreover, for extracellular concentrations >or=10 microM, TOCs also showed a significant cytotoxic effects due mainly to necrosis, while apoptosis was negligible. Gamma-TOC (the form showing preferential cell uptake and lowest unspecific cytotoxicity) was the most effective inhibitor of cell cycle progression (arrest in G0/G1 phase) leading to lowered expression of cyclin E and cyclin-dependent kinases 2 and 4 and overexpression of p27 (specific inhibitor of S-phase entering). According to these signals, activated ERK1/2 and PKC upstream and Rb phosphorylation downstream were decreased. In conclusion, within TOCs the gamma form exerts the most potent and specific control of cell cycle progression in C6 cells (cytostatic effect). This suggests a chemopreventive role of this form of vitamin E in gliomas.
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PMID:Antiproliferative effects of tocopherols (vitamin E) on murine glioma C6 cells: homologue-specific control of PKC/ERK and cyclin signaling. 1684 27

Renal tight junctions (TJ) play a central role in modulating the paracellular pathway. We examined the function, quantity and distribution of TJ proteins: occludin and claudin-2 (cln-2), on proximal tubule in a model of acute renal failure (ARF) associated with oxidative damage. Since ERK1/2-p modulates TJ integrity, we studied their participation in dichromate (Cr(6+)) toxicity. We evaluated whether co-administration of the antioxidant alpha-tocopherol (alpha-TOC) prevents Cr(6+) toxicity in TJ. Female Wistar rats received potassium dichromate 15 mg/kg, s.c. (5.3 mg/kg of Cr(6+)) single dose, with or without alpha-TOC (125 mg/kg, p.o., daily). Two and 7 days after Cr(6+) treatment, oxidative damage was assessed by renal lipid peroxidation (LPO), proximal function was estimated by sodium and glucose fractional excretions. Occludin, cln-2, and ERK1/2-p were detected by immunofluorescence and Western blot. ARF induced by Cr(6+) provoked augment in the sodium and glucose urinary looses, increases in occludin quantity (6.6- and 15-fold on days 2 and 7, respectively) and the mislocation of cln-2. Electrophoresis migration showed a higher molecular weight band only in the Cr(6+)-administered groups, suggesting occludin hyperphosphorylation. Alpha-TOC treatment diminished the LPO, improved tubular function, and preserved TJ location and expression. In summary, we show disruption of occludin and cln-2 in ARF induced by Cr(6+)-intoxication. This study provides evidence of the beneficial effect of alpha-TOC on TJ structure and function undergoing oxidative damage, and we suggest the participation of ERK1/2 in the mechanisms leading to protection by the antioxidant.
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PMID:The protective effect of alpha-tocopherol against dichromate-induced renal tight junction damage is mediated via ERK1/2. 1976 76