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Models for study in cell culture of 20S proteasomal modulators obtained from former in vitro screening

Grant number: 06/06969-0
Support Opportunities:Regular Research Grants
Duration: April 01, 2007 - March 31, 2009
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Marilene Demasi
Grantee:Marilene Demasi
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


The aim of present proposal is to continue the former Bioprospecta project entitled: “Screening for specific proteasome inhibitors followed by the determination of proapoptotic and antitumoral properties in cell culture”, (04/07636-9). In that project, it was performed the in vitro screening for catalytic proteasomal modifiers. So far, at least two compounds are already purified and their structures solved and a third one is being purified. Results obtained with one of the purified compounds together to those obtained from in vivo models by coworkers in Instituto Butantan were combined and a patent was submitted to the Brazilian office INPI. The goal in the present proposal is to establish protocols to better explore the effects observed thus far. Proposed protocols are based on different cellular models for further studies upon the effects of proteasomal modulators, such as: (1) studies on the pro-apoptotic effect of proteasomal inhibitors in tumoral cell lines by the determination of levels and activity of proteins involved in the apoptotic cascade; (2) effect upon immuno response of proteasomal mixed-modifiers in dendritic cells and, (3) a model for studies on the ability of proteasomal activators to avoid the accumulation of oxidatively modified proteins or to prevent the formation of insoluble aggregates. It is noteworthy that, one of the purified compounds might be useful for this purpose according to our preliminary results. The latter goal would be a model related to neurodegenerative diseases. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DEMASI, MARILENE; PIASSA FILHO, GILBERTO M.; CASTRO, LEANDRO M.; FERREIRA, JULIANA C.; RIOLI, VANESSA; FERRO, EMER S.. Oligomerization of the cysteinyl-rich oligopeptidase EP24.15 is triggered by S-glutathionylation. Free Radical Biology and Medicine, v. 44, n. 6, p. 1180-1190, . (04/04933-2, 06/06969-0)
DAL VECHIO, FRANCISCO H.; CERQUEIRA, FERNANDA; AUGUSTO, OHARA; LOPES, ROBSON; DEMASI, MARILENE. Peptides that activate the 20S proteasome by gate opening increased oxidized protein removal and reduced protein aggregation. Free Radical Biology and Medicine, v. 67, p. 304-313, . (06/06969-0)
DEMASI, M.; FELICIO, A. L.; PACHECO, A. O.; LEITE, H. G.; LIMA, C.; ANDRADE, L. H.. Studies on terrein as a new class of proteasome inhibitors. Journal of the Brazilian Chemical Society, v. 21, n. 2, p. 299-U187, . (06/06969-0)

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