Inhibition of PI3K/Akt/mTOR pathway by ammonium chloride induced apoptosis and autophagy in MAC-T cell

Feng, Luping; Liao, Hang; Liu, Jingsong; Xu, Chunmei; Zhong, Kai; Zhu, Hong-Jian; Guo, Shuang; Guo, Yujie; Han, Liqiang; Li, Heping; Wang, Yueying

doi:10.1016/j.rvsc.2021.01.020

Cited by 16 publications

(17 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In comparison to our work, 50 mM lactate is the point at which the growth rate is 14% lower than μ max . As for ammonium, Feng et al exposed primary bovine MAC‐T cells to 4 mM ammonium chloride, resulting in an apoptotic cell ratio of 1.8 compared to a ratio of 0.5 for the control 44 . Although a seemingly low concentration caused a higher apoptotic cell ratio, in relation to our work, 4 mM ammonium is the concentration at which the growth rate is 13% lower than μ max .…”

Section: Discussionsupporting

confidence: 49%

“…As for ammonium, Feng et al exposed primary bovine MAC-T cells to 4 mM ammonium chloride, resulting in an apoptotic cell ratio of 1.8 compared to a ratio of 0.5 for the control. 44 Although a seemingly low In another scenario, we maintain a recycle flow rate of 2.0 mL/min and increase the effective porosity with all other parameters remaining the same. We determine a new chamber constant, K cQ , of 1.29 cm 1.5 , and find that increasing effective porosity results in a smaller ideal chamber radius.…”

Section: Reactor Sizingmentioning

confidence: 99%

See 1 more Smart Citation

Development of a centrifugal bioreactor for rapid expansion of CD8 cytotoxic T cells for use in cancer immunotherapy

Kaiphanliam,

Fraser‐Hevlin,

Barrow

et al. 2023

Biotechnology Progress

View full text Add to dashboard Cite

One of the current difficulties limiting the use of adoptive cell therapy (ACT) for cancer treatment is the lack of methods for rapidly expanding T cells. As described in the present report, we developed a centrifugal bioreactor (CBR) that may resolve this manufacturing bottleneck. The CBR operates in perfusion by balancing centrifugal forces with a continuous feed of fresh medium, preventing cells from leaving the expansion culture chamber while maintaining nutrients for growth. A bovine CD8 cytotoxic T lymphocyte (CTL) cell line specific for an autologous target cell infected with a protozoan parasite, Theileria parva, was used to determine the efficacy of the CBR for ACT purposes. Batch culture experiments were conducted to predict how CTLs respond to environmental changes associated with consumption of nutrients and production of toxic metabolites, such as ammonium and lactate. Data from these studies were used to develop a kinetic growth model, allowing us to predict CTL growth in the CBR and determine the optimal operating parameters. The model predicts the maximum cell density the CBR can sustain is 5.5 × 107 cells/mL in a single 11‐mL conical chamber with oxygen being the limiting factor. Experimental results expanding CTLs in the CBR are in 95% agreement with the kinetic model. The prototype CBR described in this report can be used to develop a CBR for use in cancer immunotherapy.

show abstract

Section: Discussionsupporting

confidence: 49%

Section: Reactor Sizingmentioning

confidence: 99%

Development of a centrifugal bioreactor for rapid expansion of CD8 cytotoxic T cells for use in cancer immunotherapy

Kaiphanliam,

Fraser‐Hevlin,

Barrow

et al. 2023

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…TLR-4, which can recognize uremic toxins and infections, shows reduced levels in HD patients due to the influx of impurities from the dialysate compartment and cytoskeletal stresses from the roller pump (39). PI3K-Akt-mTOR and TNF pathways are strongly associated with the proliferation of naive and memory T cells (40)(41)(42). PI3K/mTOR inhibitor BEZ235 blocks T cell activation by inducing cell cycle arrest in G0/G1 phase (40).…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA and ATAC Sequencing Reveal Hemodialysis-Related Immune Dysregulation of Circulating Immune Cell Subpopulations

Jiang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundAn increased risk of infection, malignancy, and cardiovascular diseases in maintenance hemodialysis patients is associated with hemodialysis-related immunity disturbances. Although defects in T-lymphocyte-dependent immune responses and preactivation of antigen-presenting cells have been documented in hemodialysis patients, the effects of long-term hemodialysis on the transcriptional program and chromosomal accessibility of circulating immune cell subpopulations remain poorly defined.MethodsWe integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to characterize the transcriptome profiles of peripheral mononuclear cells (PBMCs) from healthy controls and maintenance hemodialysis patients. Validation of differentially expressed genes in CD4+ T cells and monocytes were performed by magnetic bead separation and quantitative real-time PCR.ResultsWe identified 16 and 15 PBMC subgroups in scRNA-seq and scATAC-seq datasets, respectively. Hemodialysis significantly suppressed the expression levels of T cell receptor (TCR) genes in CD4+ T cell subsets (e.g., TRAV4, CD45, CD3G, CD3D, CD3E) and major histocompatibility complex II (MHC-II) pathway-related genes in monocytes (HLA-DRB1, HLA-DQA2, HLA-DQA1, HLA-DPB1). Downstream pathways of TCR signaling, including PI3K-Akt-mTOR, MAPK, TNF, and NF-κB pathways, were also inhibited in CD4+ T cell subpopulations during the hemodialysis procedure. Hemodialysis altered cellular communication patterns between PBMC subgroups, particularly TGF-TGFBR, HVEM-BTLA, and IL16-CD4 signalings between CD4+ T cells and monocytes. Additionally, we found that hemodialysis inhibited the expression of AP-1 family transcription factors (JUN, JUND, FOS, FOSB) by interfering with the chromatin accessibility profile.ConclusionsOur study provides a valuable framework for future investigations of hemodialysis-related immune dysregulation and identifies potential therapeutic targets for reconstituting the circulating immune system in maintenance hemodialysis patients.

show abstract

“…NH 3 activates the p53 signal and mitochondrial apoptosis, as well as increases the number of apoptotic cells, leading to the apoptosis of mammary epithelial cells in dairy cows (10). Previous studies by our group demonstrated that NH 3 may induce inflammatory responses, autophagy and apoptosis, as well as inhibit the proliferation of bovine mammary epithelial cells (11).…”

Section: Introductionmentioning

confidence: 92%

Sirtuin 5 alleviates apoptosis and autophagy stimulated by ammonium chloride in bovine mammary epithelial cells

He,

Feng,

Yang

et al. 2024

Exp Ther Med

Self Cite

View full text Add to dashboard Cite

Ammonia (NH 3 ) is an irritating and harmful gas that affects cell apoptosis and autophagy. Sirtuin 5 (SIRT5) has multiple enzymatic activities and regulates NH 3 -induced autophagy in tumor cells. In order to determine whether SIRT5 regulates NH 3 -induced bovine mammary epithelial cell apoptosis and autophagy, cells with SIRT5 overexpression or knockdown were generated and in addition, bovine mammary epithelial cells were treated with SIRT5 inhibitors. The results showed that SIRT5 overexpression reduced the content of NH 3 and glutamate in cells by inhibiting glutaminase activity in glutamine metabolism, and reduced the ratio of ADP/ATP. The results in the SIRT5 knockdown and inhibitor groups were comparable, including increased content of NH 3 and glutamate in cells by activating glutaminase activity, and an elevated ratio of ADP/ATP. It was further confirmed that SIRT5 inhibited the apoptosis and autophagy of bovine mammary epithelial cells through reverse transcription-quantitative PCR, western blot, flow cytometry with Annexin V FITC/PI staining and transmission electron microscopy. In addition, it was also found that the addition of LY294002 or Rapamycin inhibited the PI3K/Akt or mTOR kinase signal, decreasing the apoptosis and autophagy activities of bovine mammary epithelial cells induced by SIRT5-inhibited NH 3 . In summary, the PI3K/Akt/mTOR signal involved in NH 3 -induced cell autophagy and apoptosis relies on the regulation of SIRT5. This study provides a new theory for the use of NH 3 to regulate bovine mammary epithelial cell apoptosis and autophagy, and provides guidance for improving the health and production performance of dairy cows.

show abstract

Inhibition of PI3K/Akt/mTOR pathway by ammonium chloride induced apoptosis and autophagy in MAC-T cell

Cited by 16 publications

References 54 publications

Development of a centrifugal bioreactor for rapid expansion of CD8 cytotoxic T cells for use in cancer immunotherapy

Development of a centrifugal bioreactor for rapid expansion of CD8 cytotoxic T cells for use in cancer immunotherapy

Single-Cell RNA and ATAC Sequencing Reveal Hemodialysis-Related Immune Dysregulation of Circulating Immune Cell Subpopulations

Sirtuin 5 alleviates apoptosis and autophagy stimulated by ammonium chloride in bovine mammary epithelial cells

Contact Info

Product

Resources

About