Project description:Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified. Experiment Overall Design: Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified.

Project description:Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified Experiment Overall Design: Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified

Project description:Objective: To determine the oxidative stress during cycles of chemotherapy in patients after surgery for colorectal cancer, with or without oral zinc supplementation. Subjects: Twenty four adults from both genders participated in this study. All patients underwent stage II, III or IV colorectal cancer surgical resection and were starting chemotherapy in HCFMRP- USP. Patients were randomized into two groups. The first one (QTx-Zn Group, n=10) received 70 mg/d of zinc orally and the second one received placebo (QTx-Placebo Group, n=14) for 16 weeks. The study also included 30 healthy volunteers matched for age, gender and socioeconomic status, who received 70 mg/d of zinc supplement (Control-Zn Group, n=21) or placebo (Control-Placebo Group, n=9) for 16 weeks. Methods: The questionnaires about dietary intake (semiquantitative food frequency and food record), fatigue and quality of life (FACIT-F) and questionnaires that assess the side effects of chemotherapy (CTCAE) were evaluated. Anthropometry and bioelectrical impedance measurements were made. Blood collection was performed before the 1st, 2nd, 3rd and 4th cycles of chemotherapy (median duration of 21 days among cicles). Routine laboratory tests, vitamin E and markers anti and pro-oxidants (MDA, SOD, GPx and isoprostane) ere determined. The control group underwent the same procedures, except for chemotherapy. A longitudinal linear mixed effects model was adjusted for each of the variables of interest. The models were fitted using PROC MIXED of SAS version 9 (SAS, CARY, NC, USA). To analyze the association of categorical variables in the different items of the CTCAE, the investigators used the Fisher exact test. Results: The oral zinc supplementation was sufficient to increase plasma levels of zinc and did not alter food intake, body composition and routine laboratory evaluation of patients undergoing chemotherapy for colorectal cancer. Compared with QTx-Placebo Group, QTx-Zn Group showed lower prevalence of complaint on the salivary gland (17 vs. 75%). Fatigue (43 ± 6 vs. 36 ± 13) and quality of life (126 ± 160 vs. 116 ± 27) has become worst in the period between the 1st and 4th cycles of QTx in QTx-Placebo Group. When compared with QTx-Placebo Group, QTx-Zn Group had higher values of SOD before the 1st (2297 ± 503 vs. 1604 ± 352 USOD/g Hb), 2nd (2037 ± 515 vs. 1712 ± 417 USOD/g Hb) and 4th (2202 ± 323 vs. 1821 ± 360 USOD/g Hb) cycles of QTx. GPx values decreased in QTx-Zn Group before the 3rd cycle of QTx (48.5 ± 7.0 vs. 54.3 ± 2.3 mol NADPH/min/gHb). Conclusions: These data suggest that zinc supplementation reduces complaints related to the change in salivary gland, preserving the quality of life and preventing the worsening of fatigue. The increase in SOD can be attributed to zinc supplementation per se, whereas this mineral is a cofactor that endogenous antioxidant enzyme. The highest activity of SOD increases the production of H2O2, whose detoxification involves the participation of GPx, justifying its reduction. There were no changes in plasma levels of vitamin E, MDA and isoprostane during the study period. Considering the values of MDA and isoprostane, the data indicate that regardless of zinc supplementation, the lipid peroxidation of the cell membrane was unchanged during chemotherapy.

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Zinc effect on mice

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