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Ramon Rosal

Publications and source records attributed to Ramon Rosal.

4 recordsLinked to original sources
PubMed2005

The role of alpha-helical structure in p53 peptides as a determinant for their mechanism of cell death: necrosis versus apoptosis.

Peptides derived from the N-terminal and C-terminal regions of the p53 tumor suppressor protein, linked to the membrane transduction domain of Antennapedia, have both been found to have significant cytotoxic effects selectively in human cancer cells. However, the N-terminal and C-terminal p53 peptides apparently display very different mechanisms for their anticancer effects. These differential effects can be attributed to dissimilar abilities to form distinctive 3-dimensional structures in extracellular-matrix-like aqueous solution that enable unique and selective cancer cell membrane penetration and effect. N-terminally based p53 peptides, with their ability to form distinctive S-shaped helix-loop-helix structures, are able to rapidly disrupt cancer cell membranes via toroidal-like pore formation causing necrosis; conversely, C-terminally based p53 peptides, due to their more random coil configuration, can be transduced across cancer cell membranes and bind to its intracellular target to cause a Fas pathway mechanism of apoptosis.

Apoptosis↗
PubMed2004

NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells.

We have recently found that a peptide from the mdm-2 binding domain of the p53 protein induced rapid membranolytic necrosis of a variety of different human cancer cell lines. To determine the role of solution structure in this peptide's selective and rapid tumor membrane disruptive behavior, we have performed two-dimensional NMR on a 32-residue sequence called PNC-27, in both an aqueous cytosolic-like and a mixed organic membrane-mimetic solution environment. In an aqueous milieu, PNC-27 contains three alpha-helical domains connected by loop structures, forming an S shape, and another similar structure with less helical structure. In a solution environment simulating a membrane, the helical domains found in water increase in length, forming three classes of structures, all of which form a U-shaped helix-coil-helix ensemble. In both solvent systems, this peptide forms amphipathic structures such that its hydrophobic residues coalesce on one face while the polar residues aggregate on the opposite face. The ability to form these unique structures in these two solution environments may allow the PNC-27 peptide to selectively and rapidly disrupt cancer cell membranes.

Amino Acid Motifs↗
PubMed2003

Polymorphisms for vinyl chloride metabolism in French vinyl chloride workers.

Genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) have been shown to influence the degree of genetic damage in Taiwanese workers exposed to the carcinogen - vinyl chloride(VC). Certain French VC workers have been found to express biomarkers of mutant forms of cancer-related proteins (ras-p21 and p53) that have been related to their exposure. ALDH2 and CYP2E1 polymorphisms were investigated in 211 of these workers in an attempt to correlate differences in VC metabolic capacity with differences in the presence of these biomarkers. All of the workers were found to have the normal, wild-type ALDH2 gene, and none of them were found to be homozygous for the variant CYP2E1 allele. Sixteen workers were found to be heterozygous for the variant CYP2E1 allele. After adjusting for age, smoking, drinking and cumulative VC exposure, the odds ratio for the presence of either the mutant ras-p21 or the mutant p53 biomarker in these heterozygous workers was found to be statistically significantly increased in comparison to their homozygous, wild-type counterparts (OR = 5.05; 95% CI = 1.10-23.25). However, as opposed to the case in Taiwanese workers, these polymorphisms are relatively uncommon, and thus differences in ALDH2 and CYP2E1 can account for only a small proportion of the variability in mutagenic response to VC exposure in a Caucasian population.

Adult↗