Browsing by Subject "Fenton reaction"

Now showing 1 - 3 of 3
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    Acid–base Homeostasis and Implications to the Phenotypic Behaviors of Cancer
    (Elsevier, 2023) Zhou, Yi; Chang, Wennan; Lu, Xiaoyu; Wang, Jin; Zhang, Chi; Xu, Ying; Medical and Molecular Genetics, School of Medicine
    Acid-base homeostasis is a fundamental property of living cells, and its persistent disruption in human cells can lead to a wide range of diseases. In this study, we conducted a computational modeling analysis of transcriptomic data of 4750 human tissue samples of 9 cancer types in The Cancer Genome Atlas (TCGA) database. Built on our previous study, we quantitatively estimated the average production rate of OH- by cytosolic Fenton reactions, which continuously disrupt the intracellular pH (pHi) homeostasis. Our predictions indicate that all or at least a subset of 43 reprogrammed metabolisms (RMs) are induced to produce net protons (H+) at comparable rates of Fenton reactions to keep the pHi stable. We then discovered that a number of well-known phenotypes of cancers, including increased growth rate, metastasis rate, and local immune cell composition, can be naturally explained in terms of the Fenton reaction level and the induced RMs. This study strongly suggests the possibility to have a unified framework for studies of cancer-inducing stressors, adaptive metabolic reprogramming, and cancerous behaviors. In addition, strong evidence is provided to demonstrate that a popular view that Na+/H+ exchangers along with lactic acid exporters and carbonic anhydrases are responsible for the intracellular alkalization and extracellular acidification in cancer may not be justified.
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    Elucidating the Functional Roles of Long Non-Coding RNAs in Alzheimer’s Disease
    (MDPI, 2024-08-25) Huang, Zhenyu; Chen, Qiufen; Mu, Xuechen; An, Zheng; Xu, Ying; Medicine, School of Medicine
    Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by cognitive decline and neuronal loss, representing a most challenging health issue. We present a computational analysis of transcriptomic data of AD tissues vs. healthy controls, focused on the elucidation of functional roles played by long non-coding RNAs (lncRNAs) throughout the AD progression. We first assembled our own lncRNA transcripts from the raw RNA-Seq data generated from 527 samples of the dorsolateral prefrontal cortex, resulting in the identification of 31,574 novel lncRNA genes. Based on co-expression analyses between mRNAs and lncRNAs, a co-expression network was constructed. Maximal subnetworks with dense connections were identified as functional clusters. Pathway enrichment analyses were conducted over mRNAs and lncRNAs in each cluster, which served as the basis for the inference of functional roles played by lncRNAs involved in each of the key steps in an AD development model that we have previously built based on transcriptomic data of protein-encoding genes. Detailed information is presented about the functional roles of lncRNAs in activities related to stress response, reprogrammed metabolism, cell polarity, and development. Our analyses also revealed that lncRNAs have the discerning power to distinguish between AD samples of each stage and healthy controls. This study represents the first of its kind.
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    Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name
    (Elsevier, 2019) Sun, Huiyan; Chen, Liang; Cao, Sha; Liang, Yanchun; Xu, Ying; Biostatistics, School of Public Health
    It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons.