PKC-δ mediates TCDD-induced apoptosis of chondrocyte in ROS-dependent manner

Lee, Hyun-Gyo; Yang, Jae‐Ho

doi:10.1016/j.chemosphere.2010.08.045

Cited by 18 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are consistent with the previous reports that both ROS and NO play important roles in mediation of chondrocyte apoptosis. 23,29,30 The apoptosis-inducing effects observed in in vitro systems may not be pathologically implicated as inducers of joint diseases such as arthritis. Therefore, caution must be taken in interpretation of in vitro data regarding their pathophysiological relevance.…”

Section: Discussionmentioning

confidence: 97%

PCB126 induces apoptosis of chondrocytes via ROS-dependent pathways

Lee

Yang

2012

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 97%

PCB126 induces apoptosis of chondrocytes via ROS-dependent pathways

Lee

Yang

2012

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

show abstract

“…Consistently, previous studies also indicated TCDD induced inhibition of de novo fatty acid biosynthesis and β-oxidation. 39,40 Interestingly, activation of AHR by single injection of β-naphthoflavone (BNF) into mouse and primary human hepatocytes was found to attenuate the expression of lipogenic genes including Scd1 , Acaca , and Fasn ), through a DRE-independent mechanism, indicating that AHR plays a key role in the inhibition of fatty acid synthesis in mice and humans. 41 …”

Section: Discussionmentioning

confidence: 99%

Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice

Zhang

Hatzakis

Nichols

et al. 2015

Environ. Sci. Technol.

View full text Add to dashboard Cite

Environmental exposure to dioxins and dioxin-like compounds poses a significant health risk for human health. Developing a better understanding of the mechanisms of toxicity through activation of the aryl hydrocarbon receptor (AHR) is likely to improve the reliability of risk assessment. In this study, the AHR-dependent metabolic response of mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF) were assessed using global 1H nuclear magnetic resonance (NMR)-based metabolomics and targeted metabolic profiling of extracts obtained from serum and liver. 1H NMR analyses revealed that TCDF exposure suppressed gluconeogenesis and glycogenolysis, stimulated lipogenesis, and triggered inflammatory gene expression in an Ahr-dependent manner. Targeted analyses using gas chromatography mass spectrometry showed TCDF treatment altered the ratio of unsaturated/saturated fatty acids. Consistent with this observation, an increase in hepatic expression of stearoyl coenzyme A desaturase 1 was also observed. In addition, TCDF exposure resulted in inhibition of de novo fatty acid biosynthesis manifested by down-regulation of acetyl-CoA, malonyl-CoA and palmitoyl-CoA metabolites and related mRNA levels. In contrast, no significant changes in the levels of glucose and lipid were observed in serum and liver obtained from Ahr-null mice following TCDF treatment, thus strongly supporting the important role of the AHR in mediating the metabolic effects seen following TCDF exposure.

show abstract

“…Reduction in the level of Ca 2+ within the cytosol (the cellular compartment that contains PKC) does not occur until at least 10 minutes postantigen exposure (Weatherly et al, 2018) and does not reach~20% inhibition (area under the curve) until 15 minutes (and~50% inhibition until 1 hour) (Weatherly et al, 2018). Thus, even though PKC activity is robustly stimulated by antigen within 10 minutes, it is unaffected by TCS ( Figure 1A), likely both due to the longer time frame required (>10 minutes) for TCS to inhibit cytosolic Ca 2+ robustly (Weatherly et al, 2018) and due to the TCS stimulation of ROS (Weatherly et al, 2018) leading to stimulation of ROS-activated PKC isoforms such as PKCδ (Cho et al, 2004;H. G. Lee & Yang, 2010;Yoshida, 2007) ( Figure 1B).…”

Section: Discussionmentioning

confidence: 98%

“…Also important to MC function are certain nPKC isoforms (PKCδ, -ε, -θ and -η), which are activated by DAG by binding to the C1 domain but which are lacking functional C2 domains and, thus, are lacking Ca 2+ responsiveness (Newton, 1995). In addition to DAG, activators of PKCδ include various agents such as phorbol esters, ultraviolet or ionizing radiation, growth factors and ROS (Lee & Yang, 2010;Yoshida, 2007). PKCβ and -δ, which belong to cPKC and nPKC, respectively, are particularly important in IgE-mediated MC degranulation (Cho, Woo, Yoon, & Kim, 2004;Nechushtan, Leitges, Cohen, Kay, & Razin, 2000;Wolfe, Chang, Rivera, & Fewtrell, 1996;Yanase et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition

Shim

Caron

Weatherly

et al. 2019

J of Applied Toxicology

View full text Add to dashboard Cite

Humans are exposed to the antimicrobial agent triclosan (TCS) through use of TCS‐containing products. Exposed tissues contain mast cells, which are involved in numerous biological functions and diseases by secreting various chemical mediators through a process termed degranulation. We previously demonstrated that TCS inhibits both Ca2+ influx into antigen‐stimulated mast cells and subsequent degranulation. To determine the mechanism linking the TCS cytosolic Ca2+ depression to inhibited degranulation, we investigated the effects of TCS on crucial signaling enzymes activated downstream of the Ca2+ rise: protein kinase C (PKC; activated by Ca2+ and reactive oxygen species [ROS]) and phospholipase D (PLD). We found that TCS strongly inhibits PLD activity within 15 minutes post‐antigen, a key mechanism of TCS mast cell inhibition. In addition, experiments using fluorescent constructs and confocal microscopy indicate that TCS delays antigen‐induced translocations of PKCβII, PKCδ and PKC substrate myristoylated alanine‐rich C‐kinase. Surprisingly, TCS does not inhibit PKC activity or overall ability to translocate, and TCS actually increases PKC activity by 45 minutes post‐antigen; these results are explained by the timing of both TCS inhibition of cytosolic Ca2+ (~15+ minutes post‐antigen) and TCS stimulation of ROS (~45 minutes post‐antigen). These findings demonstrate that it is incorrect to assume that all Ca2+‐dependent processes will be synchronously inhibited when cytosolic Ca2+ is inhibited by a toxicant or drug. The results offer molecular predictions of the effects of TCS on other mammalian cell types, which share these crucial signal transduction elements and provide biochemical information that may underlie recent epidemiological findings implicating TCS in human health problems.

show abstract

PKC-δ mediates TCDD-induced apoptosis of chondrocyte in ROS-dependent manner

Cited by 18 publications

References 40 publications

PCB126 induces apoptosis of chondrocytes via ROS-dependent pathways

PCB126 induces apoptosis of chondrocytes via ROS-dependent pathways

Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice

Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition

Contact Info

Product

Resources

About