Thymidine catabolism promotes NADPH oxidase-derived reactive oxygen species (ROS) signalling in KB and yumoto cells

Tabata, Satoshi; Yamamoto, Masayuki; Goto, Hisatsugu; Hirayama, Akiyoshi; Ohishi, Maki; Kuramoto, Takashi; Mitsuhashi, Atsushi; Ikeda, Ryuji; Haraguchi, Masanobu; Kawahara, Kohichi; Shinsato, Yoshinari; Minami, Kentaro; Saijo, Atsuro; Toyoda, Yuko; Hashimoto, Masaki; Nishioka, Yasuhiko; Sone, Saburo; Esumi, Hiroyasu; Tomita, Masaru; Soga, Tomoyoshi; Furukawa, Tatsuhiko; Akiyama, Shin Ichi

doi:10.1038/s41598-018-25189-y

Cited by 15 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such source is the pentose cycle, which provides infected cells with antioxidants that are necessary for HIV‐1 latency induction (Shytaj et al , 2020). In this regard, we show upregulation of the interconnected pyrimidine metabolism, which is involved in reactive oxygen species (ROS) production (Tabata et al , 2018). The effects of pyrimidine metabolism might underlie G6PD upregulation, which is observed during late‐productive and latent HIV‐1 infection (Shytaj et al , 2020).…”

Section: Discussionmentioning

confidence: 91%

Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress

et al. 2021

View full text Add to dashboard Cite

HIV‐1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV‐1 infection, but its role in the development and maintenance of HIV‐1 latency has not been elucidated. By combining transcriptomic, proteomic, and metabolomic analyses, we here show that transition to latent HIV‐1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD+/NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, NADPH, fueling antioxidant pathways maintaining HIV‐1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV‐1 reactivation from latency in lymphoid and myeloid cellular models. This provides a “shock and kill effect” decreasing proviral DNA in cells from people living with HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV‐1 latency that can be exploited to target latently infected cells with eradication strategies.

show abstract

Section: Discussionmentioning

confidence: 91%

Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress

et al. 2021

View full text Add to dashboard Cite

show abstract

“…TP is upregulated in many tumors and plays an important role in angiogenesis, apoptosis evasion, invasion, and metastasis, as well as in chemotherapy response [90]. Recently, Tabata and coauthors have revealed that TP activity increases NADPH levels via the pentose phosphate pathway (PPP) which activates NADPH oxidase-dependent production of ROS in cancer cells [6, 91]. Previously, it was shown that the addition of thymidine to a TP-overexpressing bladder carcinoma cell line induces cellular oxidative stress [92].…”

Section: Sources Of Ros Generation and Antioxidant Defense Systemsmentioning

confidence: 99%

ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells

Snezhkina

Kudryavtseva

Kardymon

et al. 2019

Oxidative Medicine and Cellular Longevity

616

424

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are by-products of normal cell activity. They are produced in many cellular compartments and play a major role in signaling pathways. Overproduction of ROS is associated with the development of various human diseases (including cancer, cardiovascular, neurodegenerative, and metabolic disorders), inflammation, and aging. Tumors continuously generate ROS at increased levels that have a dual role in their development. Oxidative stress can promote tumor initiation, progression, and resistance to therapy through DNA damage, leading to the accumulation of mutations and genome instability, as well as reprogramming cell metabolism and signaling. On the contrary, elevated ROS levels can induce tumor cell death. This review covers the current data on the mechanisms of ROS generation and existing antioxidant systems balancing the redox state in mammalian cells that can also be related to tumors.

show abstract

“…For antioxidant capacity, we showed that the microbial purine degradation pathway may contribute to an increase in antioxidant capacity by increasing plasma thymidine levels (P mediation = 0.02, Figure 6D). Thymidine catabolism may promote NADPH oxidase-derived reactive oxygen species to induce oxidative stress (Tabata et al, 2018). We also found that a Proteobacteria species Parasutterella excrementihominis may contribute to the decrease in plasma triglyceride by increasing plasma androsterone levels (P mediation = 0.02, Figure 6E).…”

Section: Rmt Alters Phenotypic Changes Of Newborn Calves Through Meta...mentioning

confidence: 61%

Early microbial intervention reduces diarrhea while improves later milk production in newborn calves

Shen

et al. 2023

Preprint

View full text Add to dashboard Cite

The rumen of neonatal calves is not well-developed and exhibits limited functionality. Therefore, the establishment of intestinal microbiota may play an instrumental role in their health and performance, but it has been rarely explored. Thus, we aim to explore the temporal colonization of the gut microbiome and the potential benefits of early microbial intervention in newborn calves. We followed up on the temporal dynamics of the gut microbiome and plasma metabolome in 36 newborn calves during the first two months of life and established their relationships with their health status and performance. We also evaluated whether microbiota transplantation (MT) could influence their phenotypes by modulating metabolism and its impact on later milk production performance.We showed that the composition and ecological interactions of the gut microbiome are likely to reach maturity one month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion, antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. The data from the study may help develop strategies to manipulate the gut microbiota during early life, which may be significantly relevant to the health and production of newborn calves.

show abstract

Thymidine catabolism promotes NADPH oxidase-derived reactive oxygen species (ROS) signalling in KB and yumoto cells

Cited by 15 publications

References 35 publications

Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress

Glycolysis downregulation is a hallmark of HIV‐1 latency and sensitizes infected cells to oxidative stress

ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells

Early microbial intervention reduces diarrhea while improves later milk production in newborn calves

Contact Info

Product

Resources

About