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G6PD Deficiency Enhances Oxidant-induced Cellular Senescence Through IL-8 Production
number of ovulated oocytes decreased significantly by repeated ovulation with concomitant decrease in gene expression of Tfam and NRF1 and an increase in oocytes having abnormally distributed mitochondria. Repeated ovulation decreased the amounts of mtDNA and increased the level 8-OH-dG in oocytes. All these pathologic events induced by repeated ovulation were suppressed by oral administration of L-carnitine. These results suggested that oxidative injury of oocytes and their mitochondria during repeated ovulation underlies the mechanism of ovarian aging and that L-carnitine may have therapeutic potential in ovarian aging. doi: 10.1016/j.freeradbiomed.2010.10.215
211 The Differential Avoidance of Cysteine Residues in Respiratory Chain Complexes Reflects Both Longevity and Aerobicity
and cytokine production in normal (HFF3) and G6PD-deficient (HFF1) primary human fibroblasts was examined. We found that cellular senescence is correlated with IL-8 secretion, particularly, robust IL-8 release is detected in HFF1 fibroblasts compared to HFF3 fibroblasts at basal level and continues to increase with serial H2O2 treatment. To address whether the high IL-8 level in HFF1 fibroblasts is a cell-type specific phenomenon, G6PDknockdown (Gi) cell lines were analyzed for IL-8 mRNA level, including HepG2, A549 and HL60. Consistent with our finding in fibroblasts, all Gi cells tested show elevated IL-8 expression compared to control cells at basal level. Furthermore, IL-8 secretion from Gi cells is significantly reduced by NF-κB, p38, ERK and JNK inhibitors whereas it is not affected by CXCR2 inhibitor. In conclusion, G6PD status affects cellular senescence by modulating IL-8 level through activation of downstream redoxsensitive signaling pathways. doi: 10.1016/j.freeradbiomed.2010.10.217
Mario Schindeldecker1, and Bernd Moosmann1 1 Institute for Pathobiochemistry, University of Mainz The frequency of cysteine in mitochondrially encoded proteins in long-lived animals differs significantly from that in short-lived animals: long-lived animals abstain from incorporating cysteine in a lifespan-dependent manner. To further explore this phenomenon, we have separately analyzed all respiratory chain complex subunits encoded by the mitochondrial DNA of 248 animal species. Our results indicate that complex I and complex IV show very different cysteine incorporation patterns: the almost exclusive carrier of the cysteine-lifespan correlation is complex I, whereas cysteine depletion in complex IV is essentially complete in all aerobic species and thus formally unrelated to longevity. In both complexes, cysteine usage is extensive in anaerobicparasitic species, implicating oxidative stress in the avoidance of this amino acid in the respiratory chain. The most parsimonious explanation for the differential behaviour of complex I and complex IV may be found in their relative copy numbers: in different animals and tissues, complex IV has been found to be approximately 6-8 times more highly expressed than complex I, indicating that elimination of cysteine codons in complex IV genes has a much higher effect on the protein level than elimination of cysteine codons in complex I genes. Hence, both signatures of cysteine avoidance are most likely attributable to the same causal origin, the general selection for reduced numbers of thiol groups in the inner mitochondrial membrane. Comparing the redox chemistry of thiols in hydrophobic versus hydrophilic environments, it is concluded that cysteine is avoided in respiratory chain complexes to prevent thiyl radical mediated chain-transfer reactions, potentially resulting in hydrophobic protein cross-linking or intra-protein amino acid racemization. Longevity and aerobicity appear to evoke congeneric proteomic adaptations during evolution.
doi: 10.1016/j.freeradbiomed.2010.10.216
212 G6PD Deficiency Enhances Oxidantinduced Cellular Senescence Through IL8 Production Hung-chi Yang1, Mei-Ling Cheng2, Hung-Yao Ho1, and Daniel TsunYee Chiu1,2 1 2 Chang-Gung University, Chang-Gung Memorial Hospital, Taoyuan, Taiwan G6PD-deficient cells are highly susceptible to H2O2-induced premature cellular senescence. Recent studies revealed that cellular senescence is reinforced by chemokine signaling. To test whether G6PD status affects cellular senescence through chemokine, the relationship between H2O2-induced senescence
SFRBM/SFRRI 2010
S85
211 The Differential Avoidance of Cysteine Residues in Respiratory Chain Complexes Reflects Both Longevity and Aerobicity
and cytokine production in normal (HFF3) and G6PD-deficient (HFF1) primary human fibroblasts was examined. We found that cellular senescence is correlated with IL-8 secretion, particularly, robust IL-8 release is detected in HFF1 fibroblasts compared to HFF3 fibroblasts at basal level and continues to increase with serial H2O2 treatment. To address whether the high IL-8 level in HFF1 fibroblasts is a cell-type specific phenomenon, G6PDknockdown (Gi) cell lines were analyzed for IL-8 mRNA level, including HepG2, A549 and HL60. Consistent with our finding in fibroblasts, all Gi cells tested show elevated IL-8 expression compared to control cells at basal level. Furthermore, IL-8 secretion from Gi cells is significantly reduced by NF-κB, p38, ERK and JNK inhibitors whereas it is not affected by CXCR2 inhibitor. In conclusion, G6PD status affects cellular senescence by modulating IL-8 level through activation of downstream redoxsensitive signaling pathways. doi: 10.1016/j.freeradbiomed.2010.10.217
Mario Schindeldecker1, and Bernd Moosmann1 1 Institute for Pathobiochemistry, University of Mainz The frequency of cysteine in mitochondrially encoded proteins in long-lived animals differs significantly from that in short-lived animals: long-lived animals abstain from incorporating cysteine in a lifespan-dependent manner. To further explore this phenomenon, we have separately analyzed all respiratory chain complex subunits encoded by the mitochondrial DNA of 248 animal species. Our results indicate that complex I and complex IV show very different cysteine incorporation patterns: the almost exclusive carrier of the cysteine-lifespan correlation is complex I, whereas cysteine depletion in complex IV is essentially complete in all aerobic species and thus formally unrelated to longevity. In both complexes, cysteine usage is extensive in anaerobicparasitic species, implicating oxidative stress in the avoidance of this amino acid in the respiratory chain. The most parsimonious explanation for the differential behaviour of complex I and complex IV may be found in their relative copy numbers: in different animals and tissues, complex IV has been found to be approximately 6-8 times more highly expressed than complex I, indicating that elimination of cysteine codons in complex IV genes has a much higher effect on the protein level than elimination of cysteine codons in complex I genes. Hence, both signatures of cysteine avoidance are most likely attributable to the same causal origin, the general selection for reduced numbers of thiol groups in the inner mitochondrial membrane. Comparing the redox chemistry of thiols in hydrophobic versus hydrophilic environments, it is concluded that cysteine is avoided in respiratory chain complexes to prevent thiyl radical mediated chain-transfer reactions, potentially resulting in hydrophobic protein cross-linking or intra-protein amino acid racemization. Longevity and aerobicity appear to evoke congeneric proteomic adaptations during evolution.
doi: 10.1016/j.freeradbiomed.2010.10.216
212 G6PD Deficiency Enhances Oxidantinduced Cellular Senescence Through IL8 Production Hung-chi Yang1, Mei-Ling Cheng2, Hung-Yao Ho1, and Daniel TsunYee Chiu1,2 1 2 Chang-Gung University, Chang-Gung Memorial Hospital, Taoyuan, Taiwan G6PD-deficient cells are highly susceptible to H2O2-induced premature cellular senescence. Recent studies revealed that cellular senescence is reinforced by chemokine signaling. To test whether G6PD status affects cellular senescence through chemokine, the relationship between H2O2-induced senescence
SFRBM/SFRRI 2010
S85