CCP1/Nna1 functions in protein turnover in mouse brain: Implications for cell death in Purkinje cell degeneration mice

Purkinje cell degeneration (pcd) mice have a mutation within the gene encoding cytosolic carboxypeptidase 1 (CCP1/Nna1), which has homology to metallocarboxypeptidases. To assess the function of CCP1/Nna1, quantitative proteomics and peptidomics approaches were used to compare proteins and peptides in mutant and wild-type mice. Hundreds of peptides derived from cytosolic and mitochondrial proteins are greatly elevated in pcd mouse hypothalamus, amygdala, cortex, prefrontal cortex, and striatum. However, the major proteins detected on 2-D gel electrophoresis were present in mutant and wild-type mouse cortex and hypothalamus at comparable levels, and proteasome activity is normal in these brain regions of pcd mice, suggesting that the increase in cellular peptide levels in the pcd mice is due to reduced degradation of the peptides downstream of the proteasome. Both nondegenerating and degenerating regions of pcd mouse brain, but not wild-type mouse brain, show elevated autophagy, which can be triggered by a decrease in amino acid levels. Taken together with previous studies on CCP1/Nna1, these data suggest that CCP1/Nna1 plays a role in protein turnover by cleaving proteasome-generated peptides into amino acids and that decreased peptide turnover in the pcd mice leads to cell death.-Berezniuk, I., Sironi, J., Callaway, M. B., Castro, L. M., Hirata, I. Y., Ferro, E. S., Fricker, L. D. CCP1/Nna1 functions in protein turnover in mouse brain: Implications for cell death in Purkinje cell degeneration mice. FASEB J. 24, 1813-1823 (2010). www.fasebj.org

CPDs and 6-4PPs play different roles in UV-induced cell death in normal and NER-deficient human cells

Ultraviolet (UV) light generates two major DNA lesions: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs), but the specific participation of these two lesions in the deleterious effects of UV is a longstanding question. In order to discriminate the precise role of unrepaired CPDs and 6-4PPs in UV-induced responses triggering cell death, human fibroblasts were transduced by recombinant adenoviruses carrying the CPD-photolyase or 6-4PP-photolyase cDNAs. Both photolyases were able to prevent UV-induced apoptosis in cells deficient for nucleotide excision repair (NER) to a similar extent, while in NER-proficient cells UV-induced apoptosis was prevented only by CPD-photolyase, with no effects observed when 6-4PPs were removed by the specific photolyase. These results strongly suggest that both CPDs and 6-4PPs contribute to UV-induced apoptosis in NER-deficient cells, while in NER-proficient cells, CPDs are the only lesions responsible for UV-killing, probably due to the rapid repair of 6-4PPs by NER. As a consequence, the difference in skin photosensitivity, including carcinogenesis, of most of the xeroderma pigmentosum patients and of normal people is probably not only a quantitative aspect, but depends on the type of DNA damage induced by sunlight and its rate of repair. (c) 2007 Elsevier B.V. All rights reserved.

Molecular Characterization of Propolis-Induced Cell Death in Saccharomyces cerevisiae

Propolis, a natural product of plant resins, is used by the bees to seal holes in their honeycombs and protect the hive entrance. However, propolis has also been used in folk medicine for centuries. Here, we apply the power of Saccharomyces cerevisiae as a model organism for studies of genetics, cell biology, and genomics to determine how propolis affects fungi at the cellular level. Propolis is able to induce an apoptosis cell death response. However, increased exposure to propolis provides a corresponding increase in the necrosis response. We showed that cytochrome c but not endonuclease G (Nuc1p) is involved in propolis-mediated cell death in S. cerevisiae. We also observed that the metacaspase YCA1 gene is important for propolis-mediated cell death. To elucidate the gene functions that may be required for propolis sensitivity in eukaryotes, the full collection of about 4,800 haploid S. cerevisiae deletion strains was screened for propolis sensitivity. We were able to identify 138 deletion strains that have different degrees of propolis sensitivity compared to the corresponding wild-type strains. Systems biology revealed enrichment for genes involved in the mitochondrial electron transport chain, vacuolar acidification, negative regulation of transcription from RNA polymerase II promoter, regulation of macroautophagy associated with protein targeting to vacuoles, and cellular response to starvation. Validation studies indicated that propolis sensitivity is dependent on the mitochondrial function and that vacuolar acidification and autophagy are important for yeast cell death caused by propolis.

A Survey of Fungal Contamination on Books in Public Libraries with Mechanical and Natural Ventilation

Libraries are very propitious environments for the growth of fungi. The great concentration of organic material available for these microorganisms, and often with the lack of adequate ventilation or climate control, would favour this situation. This study was conducted in 2003 to determine the predominant genera of fungi in public libraries by a survey of fungi contaminating the upper surface of books, with and without air conditioning in the city of Sao Paulo, Brazil, in the winter and summer, during the respective periods with high and low levels of airborne fungi in that city. Six libraries were chosen, located on the campus of the University of Sao Paulo, three of them with air conditioning and the other three with natural ventilation. In these six libraries, 31 genera of fungi were identified in total. The genera and frequency of contaminant fungi recovered differed significantly between the libraries with and without air conditioning and in the samples collected in the summer as opposed to the winter. Cladosporium was the most frequent in the libraries with and without air conditioning, and in the winter. Aspergillus was isolated more often in the summer.

Paracoccidioidomycosis-related mortality trend, state of Sao Paulo, Brazil: a study using multiple causes of death

Objective. To investigate mortality in which paracoccidioidomycosis appears on any line or part of the death certificate. Method. Mortality data for 1985-2005 were obtained from the multiple cause-of-death database maintained by the Sao Paulo State Data Analysis System (SEADE). Standardized mortality coefficients were calculated for paracoccidioidomycosis as the underlying cause-of-death and as an associated cause-of-death, as well as for the total number of times paracoccidioidomycosis was mentioned on the death certificates. Results. During this 21-year period, there were 1950 deaths related to paracoccidioidomycosis; the disease was the underlying cause-of-death in 1 164 cases (59.69%) and an associated cause-of-death in 786 (40.31%). Between 1985 and 2005 records show a 59.8% decline in the mortality coefficient due to paracoccidioidomycosis as the underlying cause and a 53.0% decline in the mortality as associated cause. The largest number of deaths occurred among men, in the older age groups, and among rural workers, with an upward trend in winter months. The main causes associated with paracoccidioidomycosis as the underlying cause-of-death were pulmonary fibrosis, chronic lower respiratory tract diseases, and pneumonias. Malignant neoplasms and AIDS were the main underlying causes when paracoccidioidomycosis was an associated cause-of-death. The decision tables had to be adapted for the automated processing of causes of death in death certificates where paracoccidioidomycosis was mentioned. Conclusions. Using the multiple cause-of-death method together with the traditional underlying cause-of-death approach provides a new angle on research aimed at broadening our understanding of the natural history of paracoccidioidomycosis.