Cetrimonium bromide promotes lipid clearance via TFEB-mediated autophagy-lysosome activation in hepatic cells

2021 ◽  
Author(s):  
Zhenxing Liu ◽  
Xu Wang ◽  
Zhichen Shi ◽  
Junting Xu ◽  
Jieru Lin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Disorders ◽  
Nuclear Translocation ◽  
Quaternary Ammonium Compound ◽  
Ammonium Compound ◽  
Hepatic Cells ◽  
Mtorc1 Signaling ◽  
Transcription Factor Eb ◽  
Potential Strategy ◽  
Cetrimonium Bromide

Autophagy plays a key role in the metabolism of macromolecules by the lysosomal degradative machinery. The transcription factor EB (TFEB) regulates autophagosome biogenesis and lysosome function, and promoting TFEB activity has emerged as a potential strategy for the treatment of metabolic disorders. Here, we describe that cetrimonium bromide (CTAB), a quaternary ammonium compound, promotes autophagy and lysosomal biogenesis by inducing the nuclear translocation of TFEB in hepatic cells. shRNA-mediated TFEB knockdown inhibits CTAB-induced autophagy and lysosomal biogenesis. Mechanistically, CTAB treatment inhibits the Akt-mTORC1 signaling pathway. Moreover, CTAB treatment markedly promotes lipid metabolism in both palmitate and oleate-treated HepG2 cells, and this promotion was attenuated by the depletion of TFEB. Altogether, our results indicate that CTAB activates the autophagy-lysosome pathway by inducing the nuclear translocation of TFEB via the inhibition of mTORC1 signaling. These results deepen our understanding of TFEB function and provide new insights into CTAB-mediated lipid metabolism.

scholarly journals Prevalence and Detection of qac Genes from Disinfectant-Resistant Staphylococcus aureus Isolated from Salon Tools in Ishaka Town, Bushenyi District of Uganda

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Solange Gahongayire ◽  
Adamu Almustapha Aliero ◽  
Charles Drago Kato ◽  
Alice Namatovu
Keyword(s):  
Sodium Hypochlorite ◽  
Quaternary Ammonium ◽  
Bacterial Infections ◽  
Healthcare Providers ◽  
Quaternary Ammonium Compound ◽  
Diffusion Method ◽  
Ammonium Compound ◽  
Bacterial Strains ◽  
Microbiological Methods ◽  
Phenotypic Methods

Bacterial infections are on a rise with causal-resistant strains increasing the economic burden to both patients and healthcare providers. Salons are recently reported as one of the sources for transmission of such resistant bacterial strains. The current study aimed at the identification of the prevalent bacteria and characterization of quaternary ammonium compound (qac) genes from disinfectant-resistant S. aureus isolated from salon tools in Ishaka town, Bushenyi District of Uganda. A total of 125 swabs were collected from different salon tools (combs, brushes, scissors, clippers, and shaving machines), and prevalent bacteria were isolated using standard microbiological methods. Identification of isolated bacteria was done using standard phenotypic methods including analytical profile index (API). Susceptibility patterns of the isolated bacteria to disinfectant were determined using the agar well diffusion method. Quaternary ammonium compound (qac) genes (qacA/B and qacC) associated with disinfectant resistances were detected from disinfectant-resistant S. aureus using multiplex polymerase chain reaction (PCR) and Sanger sequencing methods. Of the 125 swab samples collected from salons, 78 (62.4%) were contaminated with different bacteria species. Among the salon tools, clippers had the highest contamination of 20 (80.0%), while shaving machines had the lowest contamination of 11 (44.0%). The most prevalent bacteria identified were Staphylococcus epidermidis (28.1%) followed by S. aureus (26.5%). Of all the disinfectants tested, the highest resistance was shown with sodium hypochlorite 1%. Out of the eight (8) disinfectant-resistant S. aureus analysed for qac genes, 2 (25%) isolates (STP6 and STP9) were found to be qacA/B positive, while 2 (25%) isolates (STP8 and STP9) were found to be qacC gene positive. This study has shown that bacterial contamination of salon tools is common, coupled with resistance to disinfectants with sodium hypochlorite resistance being more common. Furthermore, observed resistance was attributed to the presence of qac genes among S. aureus isolates. A search for qac genes for disinfectant resistance from other bacteria species is recommended.

scholarly journals RIP3 impedes transcription factor EB to suppress autophagic degradation in septic acute kidney injury

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Ruizhao Li ◽  
Xingchen Zhao ◽  
Shu Zhang ◽  
Wei Dong ◽  
Li Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Nuclear Translocation ◽  
Kidney Injury ◽  
Septic Acute Kidney Injury ◽  
Transcription Factor Eb ◽  
Autophagic Degradation ◽  
Lps Treatment

AbstractAutophagy is an important renal-protective mechanism in septic acute kidney injury (AKI). Receptor interacting protein kinase 3 (RIP3) has been implicated in the renal tubular injury and renal dysfunction during septic AKI. Here we investigated the role and mechanism of RIP3 on autophagy in septic AKI. We showed an activation of RIP3, accompanied by an accumulation of the autophagosome marker LC3II and the autophagic substrate p62, in the kidneys of lipopolysaccharide (LPS)-induced septic AKI mice and LPS-treated cultured renal proximal tubular epithelial cells (PTECs). The lysosome inhibitor did not further increase the levels of LCII or p62 in LPS-treated PTECs. Moreover, inhibition of RIP3 attenuated the aberrant accumulation of LC3II and p62 under LPS treatment in vivo and in vitro. By utilizing mCherry-GFP-LC3 autophagy reporter mice in vivo and PTECs overexpression mRFP-GFP-LC3 in vitro, we observed that inhibition of RIP3 restored the formation of autolysosomes and eliminated the accumulated autophagosomes under LPS treatment. These results indicated that RIP3 impaired autophagic degradation, contributing to the accumulation of autophagosomes. Mechanistically, the nuclear translocation of transcription factor EB (TFEB), a master regulator of the lysosome and autophagy pathway, was inhibited in LPS-induced mice and LPS-treated PTECs. Inhibition of RIP3 restored the nuclear translocation of TFEB in vivo and in vitro. Co-immunoprecipitation further showed an interaction of RIP3 and TFEB in LPS-treated PTECs. Also, the expression of LAMP1 and cathepsin B, two potential target genes of TFEB involved in lysosome function, were decreased under LPS treatment in vivo and in vitro, and this decrease was rescued by inhibiting RIP3. Finally, overexpression of TFEB restored the autophagic degradation in LPS-treated PTECs. Together, the present study has identified a pivotal role of RIP3 in suppressing autophagic degradation through impeding the TFEB-lysosome pathway in septic AKI, providing potential therapeutic targets for the prevention and treatment of septic AKI.

Building a Better Quaternary Ammonium Compound (QAC): Branched Tetracationic Antiseptic Amphiphiles

ChemMedChem ◽  
2016 ◽  
Vol 11 (13) ◽  
pp. 1401-1405 ◽  
Author(s):  
Megan E. Forman ◽  
Megan C. Jennings ◽  
William M. Wuest ◽  
Kevin P. C. Minbiole
Keyword(s):  
Quaternary Ammonium ◽  
Quaternary Ammonium Compound ◽  
Ammonium Compound

Age-related blood biochemical changes (lipid metabolism) in healthy young and mature men living under the North conditions

2021 ◽  
Vol 66 (12) ◽  
pp. 728-732
Author(s):  
Inessa Vladislavovna Averyanova
Keyword(s):  
Lipid Metabolism ◽  
Cardiovascular Diseases ◽  
Lipid Profile ◽  
Metabolic Disorders ◽  
Age Groups ◽  
Photometric Method ◽  
The North ◽  
Blood Biochemical ◽  
Age Related ◽  
Younger Men

Metabolic disorders (dyslipidemias) are currently crucial since they develop cardiovascular diseases. The work was aimed at studying age dynamics and its correlation with severity of dyslipidemia in basic lipid metabolism variables (in different age groups). Materials and methods: Examinees were Caucasians born and permanently residing in Magadan region: 55 mature men and 147 young men (mean ages were 36.8±0.8 and 18.7±0.8 yr, respectively). Blood serum lipid metabolism was examined by colorimetric and photometric method using AU 680 (Beckman Coulter, USA). Results: The data of obtained lipidogram showed dependence of rise in all indicators on subjective older age with higher percentage of dyslipidemia and increase in calculated indices reflecting degree of the lipid profile atherogenicity. Conclusion: Overall, the North study revealed a safer lipid profile in group of younger men, while biochemical picture of older residents demonstrated increased values. Lipid atherogenicity is a very alarming factor in developing cardiovascular diseases, and a predictor of risks for metabolic syndrome.

scholarly journals Pentamethylquercetin Attenuates Cardiac Remodeling via Activation of the Sestrins/Keap1/Nrf2 Pathway in MSG-Induced Obese Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Jingxia Du ◽  
Wei He ◽  
Cai Zhang ◽  
Jianzhao Wu ◽  
Zhi Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cardiac Remodeling ◽  
Metabolic Disorders ◽  
Cardiac Fibrosis ◽  
Nuclear Translocation ◽  
Monosodium Glutamate ◽  
Immunofluorescent Staining ◽  
Obese Mice ◽  
Nrf2 Signaling Pathway ◽  
Obesity Cardiomyopathy

Objective. Obesity causes a variety of metabolic alterations that may contribute to abnormalities of the cardiac structure and function (obesity cardiomyopathy). In previous works, we have shown that pentamethylquercetin (PMQ) significantly improved metabolic disorders in obese mice and it inhibited pressure overload-induced cardiac remodeling in mice. However, its potential benefit in obesity cardiomyopathy remains unclear. The aim of this study was to investigate the effects of PMQ on cardiac remodeling in obese mice. Methods. We generated a monosodium glutamate-induced obese (MSG-IO) model in mice, which were treated with PMQ (5, 10, and 20 mg/kg) for 16 weeks consecutively. We examined the metabolic parameters and observed cardiac remodeling by performing cardiac echocardiography and Masson’s staining. The expression levels of molecules associated with the endogenous antioxidant system, including the sestrins/kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, were analyzed by western blotting and immunofluorescent staining. Results. We found that PMQ treatment significantly ameliorated obesity phenotypes and improved metabolic disorders in MSG-IO mice. PMQ decreased the heart wall thickness and attenuated cardiac fibrosis. Further study revealed that the protective effects of PMQ might be mediated by promoting Keap1 degradation and augmenting sestrins expression and Nrf2 nuclear translocation. Conclusion. Our findings indicated that PMQ ameliorated cardiac remodeling in obese mice by targeting the sestrins/Keap1/Nrf2 signaling pathway.

scholarly journals How cancer cells remodel lipid metabolism: strategies targeting transcription factors

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Do-Won Jeong ◽  
Seulbee Lee ◽  
Yang-Sook Chun
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Factors Associated ◽  
Modeling Techniques ◽  
Related Enzyme ◽  
Potential Strategy

AbstractReprogramming of lipid metabolism has received increasing recognition as a hallmark of cancer cells because lipid dysregulation and the alteration of related enzyme profiles are closely correlated with oncogenic signals and malignant phenotypes, such as metastasis and therapeutic resistance. In this review, we describe recent findings that support the importance of lipids, as well as the transcription factors involved in cancer lipid metabolism. With recent advances in transcription factor analysis, including computer-modeling techniques, transcription factors are emerging as central players in cancer biology. Considering the limited number and the crucial role of transcription factors associated with lipid rewiring in cancers, transcription factor targeting is a promising potential strategy for cancer therapy.

scholarly journals The role of phagocytosis-dependent activation of TFEB in the clearance of salmonella

2021 ◽  
Author(s):  
Erika Ospina Escobar
Keyword(s):  
Transcription Factor ◽  
Salmonella Typhimurium ◽  
Nuclear Translocation ◽  
Steady Increase ◽  
Phagosome Maturation ◽  
Salmonella Infection ◽  
Complex Interplay ◽  
Transcription Factor Eb ◽  
Insight Into

During phagocytosis, macrophages engulf and sequester pathogens into phagosomes. Phagosomes then fuse with acidic and degradative lysosomes to degrade the internalized pathogen. We previously demonstrated that phagocytosis of IgG-opsonized particles and non-opsonized E.coli causes activation of the Transcription Factor EB (TFEB), which enhances the expression of lysosomal genes, increases the degradative capacity of lysosomes and boosts bactericidal activity. However, pathogens like Salmonella typhimurium have evolved mechanisms to evade and/or alter phagosome maturation to promote their own survival. We investigated: i) whether pathogens like Salmonella can alter TFEB activation and ii) whether phagocytosis-dependent activation of TFEB can counteract the pathogenicity of microorganisms. Here, we show that non-viable (heat-killed) S. typhimurium, pathogenic (EHEC and UPEC) and non-pathogenic E.coli (DH5α) all caused TFEB nuclear translocation in RAW macrophages, while strikingly live S. typhimurium maintained TFEB in the cytosol in the first hours post-infection. By contrast, Salmonella mutants for ΔsifA, ΔsopD2, ΔphoP all triggered TFEB activation in the first hour of infection. However, Salmonella infection eventually triggered a steady increase in nuclear TFEB after 4 h of infection, suggesting a more complex interplay between TFEB and Salmonella infection. We dissected the importance of TFEB activation towards Salmonella survivability by pre-activating TFEB before infection within WT macrophages and macrophages with a CRISPR-based deletion of TFEB. Our work suggests that Salmonella actively interferes with TFEB signaling in order to enhance its own survival. These results could provide insight into using TFEB as a target for the clearance of infections.

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