Browsing by Subject "reactive oxygen species"

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Metabolomic and Transcriptomic Insights into How Cotton Fiber Transitions to Secondary Wall Synthesis, Represses Lignification, and Prolongs Elongation
(2015-06) Tuttle, John R.; Nah, Gyoungju; Duke, Mary V.; Alexander, Danny C.; Guan, Xueying; Song, Qingxin; Chen, Z. Jeffrey; Scheffler, Brian E.; Haigler, Candace; Nah, Gyoungju; Guan, Xueying; Song, Qingxin; Chen, Z. Jeffrey
The morphogenesis of single-celled cotton fiber includes extreme elongation and staged cell wall differentiation. Designing strategies for improving cotton fiber for textiles and other uses relies on uncovering the related regulatory mechanisms. In this research we compared the transcriptomes and metabolomes of two Gossypium genotypes, Gossypium barbadense cv Phytogen 800 and G. hirsutum cv Deltapine 90. When grown in parallel, the two types of fiber developed similarly except for prolonged fiber elongation in the G. barbadense cultivar. The data were collected from isolated fibers between 10 to 28 days post anthesis (DPA) representing: primary wall synthesis to support elongation; transitional cell wall remodeling; and secondary wall cellulose synthesis, which was accompanied by continuing elongation only in G. barbadense fiber. Results: Of 206 identified fiber metabolites, 205 were held in common between the two genotypes. Approximately 38,000 transcripts were expressed in the fiber of each genotype, and these were mapped to the reference set and interpreted by homology to known genes. The developmental changes in the transcriptomes and the metabolomes were compared within and across genotypes with several novel implications. Transitional cell wall remodeling is a distinct stable developmental stage lasting at least four days (18 to 21 DPA). Expression of selected cell wall related transcripts was similar between genotypes, but cellulose synthase gene expression patterns were more complex than expected. Lignification was transcriptionally repressed in both genotypes. Oxidative stress was lower in the fiber of G. barbadense cv Phytogen 800 as compared to G. hirsutum cv Deltapine 90. Correspondingly, the G. barbadense cultivar had enhanced capacity for management of reactive oxygen species during its prolonged elongation period, as indicated by a 138-fold increase in ascorbate concentration at 28 DPA. Conclusions: The parallel data on deep-sequencing transcriptomics and non-targeted metabolomics for two genotypes of single-celled cotton fiber showed that a discrete developmental stage of transitional cell wall remodeling occurs before secondary wall cellulose synthesis begins. The data showed how lignification can be transcriptionally repressed during secondary cell wall synthesis, and they implicated enhanced capacity to manage reactive oxygen species through the ascorbate-glutathione cycle as a positive contributor to fiber length.
p53 Impact Reactive Oxygen Species and Drug Resistance in Multiple Myeloma
(2023) Chiu, Ian; Matsui, William
Multiple myeloma (MM) is an incurable blood cancer characterized by the proliferation of malignant plasma cells. Several recurrent genetic alterations occur in MM, but mutations in the TP53 gene are associated with the worst clinical outcomes due to the rapid development of drug-resistant disease. The p53 protein, coded by the TP53 gene, is a tumor suppressor involved in coordinating responses to cellular stress, such as DNA damage, that lead to cell cycle arrest and apoptosis. Most chemotherapies lead to increased intracellular reactive oxygen species (ROS) levels, and ROS can activate p53, signal downstream of TP53, and be regulated by TP53 target genes. In MM, it is not clear whether p53 mutations impact ROS levels and whether changes in ROS are associated with drug resistance. We examined the impact of the loss of p53 via knockout of TP53 (p53KO) on ROS levels and drug sensitivity in the MM1.S myeloma cell line. We also found that baseline ROS levels were significantly lower in p53KO cells than in control cells from each MM cell line (p<0.05). Compared to wild-type cells, we also found that the IC50 of doxorubicin was approximately two-fold higher in p53KO cells (p<0.05). When cells were treated with N-acetyl cysteine (NAC), a ROS scavenger, and doxorubicin for 24 hours, ROS levels were significantly lowered compared to the doxorubicin single control cells in both control and p53KO cells (p<0.05). Furthermore, treatment with NAC significantly enhanced doxorubicin resistance (p<0.05). Our findings suggest that lower ROS levels are a characteristic of p53 loss, both before and after doxorubicin treatment, and the attenuation of ROS in p53KO cells leads to drug resistance. Overall, these studies will lead to a better understanding of the relationship between p53, ROS levels, and drug resistance and may lead to new strategies to improve the efficacy of chemotherapy in mutant p53 MM.
Uncoupling protein 3 attenuates generation of reactive oxygen species by interacting with thioredoxin 2 in the mitochondrial intermembrane space
(Arthritis Research and Therapy, 2012-02-09) Hirasaka, Katsuya; Mills, Edward M.; Kohno, Shohei; Abe, Tomoki; Ikeda, Chika; Maeda, Tasuku; Kondo, Shigetada; Maita, Ayako; Okummura, Yuushi; Nikawa, Takeshi
Poster presentation Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. It has been proposed that UCP3 reduces production of reactive oxygen species (ROS) and oxidative damage. However, the mechanisms by which UCP3 attenuates ROS production are not well understood. Here we report that UCP3 interacts with the non-processed form of thioredoxin 2 (Trx2), a redox protein that is localized in mitochondria, but not processed Trx2, which is involved in cellular responses to ROS. The hydrophilic sequences within the N-terminal tail of UCP3, which faces the intermembrane space, are necessary for binding to Trx2. In addition, Trx2 directly associated with UCP3 through a mitochondrial targeting signaling sequence, was processed in the intermembrane space, and thereby allowing redox reactions. A bimolecular fluorescence complementation analysis demonstrated that the interaction of these proteins occurs in the mitochondrial intermembrane space. Furthermore, increased UCP3 expression significantly attenuated ROS production in isolated mitochondrial without effects on membrane potential, however this effect is lost by Trx2 knock down. These results suggest that UCP3 binds to Trx2 in the mitochondrial intermembrane space and attenuates ROS production.