Hexabromocyclododecane and polychlorinated biphenyls increase resistance of hepatocellular carcinoma cells to cisplatin through the phosphatidylinositol 3-kinase/protein kinase B pathway

An, Jing; Wang, Xiu; Guo, Panpan; Zhong, Yufang; Zhang, Xinyu; Yu, Zhiqiang

doi:10.1016/j.toxlet.2014.06.025

Cited by 25 publications

(28 citation statements)

References 41 publications

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“…12,48 Furthermore, mitochondrial dysfunction can activate PI3K/AKT signalling, which is crucial for inflammation in RA FLSs. 50,51 In this study, we found that treatment with mdivi-1 or DNM1L silencing effectively decreased ROS production and LC3B-related autophagy in FLSs, extending the previous observation in osteoblasts. 50,51 In this study, we found that treatment with mdivi-1 or DNM1L silencing effectively decreased ROS production and LC3B-related autophagy in FLSs, extending the previous observation in osteoblasts.…”

Section: Discussionsupporting

confidence: 88%

“…17,49 In addition, the activated AKT can induce IKK phosphorylation and NF-κB, which is down-regulated by NFKBIA. 50,51 In this study, we found that treatment with mdivi-1 or DNM1L silencing effectively decreased ROS production and LC3B-related autophagy in FLSs, extending the previous observation in osteoblasts. 42 Moreover, DNM1L deficiency also mitigated the IL-1β-induced AKT and IKK phosphorylation and NF-κBp65 nuclear translocation, but increased NFKBIA expression in RA FLS.…”

Section: Discussionsupporting

confidence: 88%

“…After being washed, the cells were probed with anti-NF-κBp65 (1: 50) at 4°C overnight, stained with Cy3-conjugated secondary antibody…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

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Inhibition of DNM1L and mitochondrial fission attenuates inflammatory response in fibroblast‐like synoviocytes of rheumatoid arthritis

Wang

Chen

Fan

et al. 2019

J Cellular Molecular Medi

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Mitochondrial fission and fusion are important for mitochondrial function, and dynamin 1-like protein (DNM1L) is a key regulator of mitochondrial fission. We investigated the effect of mitochondrial fission on mitochondrial function and inflammation in fibroblast-like synoviocytes (FLSs) during rheumatoid arthritis (RA). DNM1L expression was determined in synovial tissues (STs) from RA and non-RA patients.FLSs were isolated from STs and treated with a DNM1L inhibitor (mdivi-1, mitochondrial division inhibitor 1) or transfected with DNM1L-specific siRNA. Mitochondrial morphology, DNM1L expression, cell viability, mitochondrial membrane potential, reactive oxygen species (ROS), apoptosis, inflammatory cytokine expression and autophagy were examined. The impact of mdivi-1 treatment on development and severity of collagen-induced arthritis (CIA) was determined in mice. Up-regulated DNM1L expression was associated with reduced mitochondrial length in STs from patients with RA and increased RA severity. Inhibition of DNM1L in FLSs triggered mitochondrial depolarization, mitochondrial elongation, decreased cell viability, production of ROS, IL-8 and COX-2, and increased apoptosis. DNM1L deficiency inhibited IL-1βmediated AKT/IKK activation, NF-κBp65 nuclear translocation and LC3B-related autophagy, but enhanced NFKBIA expression. Treatment of CIA mice with mdivi-1 decreased disease severity by modulating inflammatory cytokine and ROS production. Our major results are that up-regulated DNM1L and mitochondrial fission promoted survival, LC3B-related autophagy and ROS production in FLSs, factors that lead to inflammation by regulating AKT/IKK/NFKBIA/NF-κB signalling. Thus, inhibition of DNM1L may be a new strategy for treatment of RA. K E Y W O R D Sdynamin 1-like protein, fibroblast-like synoviocyte, inflammation, mitochondrial fission, rheumatoid arthritis | 1517 WANG et Al.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 88%

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Inhibition of DNM1L and mitochondrial fission attenuates inflammatory response in fibroblast‐like synoviocytes of rheumatoid arthritis

Wang

Chen

Fan

et al. 2019

J Cellular Molecular Medi

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“…38 Our result was consistent with a recent study identifying an induced p38 activity, required for paxillin phosphorylation and focal adhesion assembly, during the dysregulation of vascular endothelial integrity induced by a quinone type of PCB. 19 Although SB203580 was also known to inhibit PKB activity 39 and Aroclor1254 has been reported to increase the phosphorylation of PKB in hepatocellular carcinoma cells, 40 the phosphorylation level of PKB in cultured SCs did not show significant difference after Aroclor1254 exposure, which further confirmed the counteraction of SB203580 against Aroclor1254 herein was due to its inhibition on p38 MAPK.…”

Section: Discussionmentioning

confidence: 81%

Aroclor1254 disrupts the blood–testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway

Jia

et al. 2017

Cell Death Dis

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The blood–testis barrier (BTB) constituted by coexisting junction apparatus between Sertoli cells (SCs) plays an important role in spermatogenesis, which is a known target of various environmental toxicants. The commercial polychlorinated biphenyls mixture, Aroclor1254, has been shown to impair male reproduction by decreasing sperm count and affecting SC metabolism. This study was designed to investigate the effects of Aroclor1254 on the BTB integrity and elucidate the underlying mechanisms. We found that Aroclor1254 treatment in rats (1 or 3 mg/kg per day for 21 consecutive days) and in primary cultured SCs (5 or 10 μg/ml for 48 h) could induce BTB disruption via p38 MAPK pathway, concurrently with increments in junction proteins (JAM-A, N-cadherin, and β-catenin) endocytosis, and occludin ubiquitination. Either inhibition of caveolin-dependent membrane protein internalization by cholesterol oxidase or silencing E3 ubiquitine ligase Itch by small interfering RNA could partially counteract the effects of Aroclor1254 on the barrier function of cultured SCs. These results demonstrate that Aroclor1254 disrupts the BTB function by promoting the caveolin-dependent endocytosis and ubiquitine–proteasome degradation of junction proteins through the p38 MAPK pathway, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.

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“…To our knowledge, this is the first study to demonstrate a potential impact of PCBs on mtor in an organismal exposure scenario. However, there have been recent findings, gathered from exposed adipocytes (Kim et al, 2012) and liver carcinoma cells (An et al, 2014), which identify mTOR as a potential target of PCBs. In those studies, alterations in mTOR expression were observed in cells exposed to the NDL PCB congener 153 or Aroclor 1254 (predominantly comprised of ortho rich NDL PCBs), but these effects were not seen in cells exposed to TCDD.…”

Section: 0 Results and Discussionmentioning

confidence: 99%

Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA

et al. 2015

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Atlantic killifish (Fundulus heteroclitus) thrive in New Bedford Harbor (NBH), MA, highly contaminated with polychlorinated biphenyls (PCBs). Resident killifish have evolved tolerance to dioxin-like (DL) PCBs, whose toxic effects through the aryl hydrocarbon receptor (AhR) are well studied. In NBH, non-dioxin like PCBs (NDL PCBs), which lack activity toward the AhR, vastly exceed levels of DL congeners yet how killifish counter NDL toxic effects has not been explored. In mammals and fish, NDL PCBs are potent activators of ryanodine receptors (RyR), Ca2+ release channels necessary for a vast array of physiological processes. In the current study we compared the expression and function of RyR related pathways in NBH killifish with killifish from the reference site at Scorton Creek (SC, MA). Relative to the SC fish, adults from NBH displayed increased levels of skeletal muscle RyR1 protein, and increased levels of FK506-binding protein 12 kDa (FKBP12), an accessory protein essential for NDL PCB-triggered changes in RyR channel function. In accordance with increased RyR1 levels, NBH killifish displayed increased maximal ligand binding, increased maximal response to Ca2+ activation and increased maximal response to activation by the NDL PCB congener PCB 95. Compared to SC, NBH embryos and larvae had increased levels of mtor and ryr2 transcripts at multiple stages of development, and generations, while levels of serca2 were decreased at 9 days post-fertilization in the F1 and F2 generations. These findings suggest that there are compensatory and heritable changes in RyR mediated Ca2+ signaling proteins or potential signaling partners in NBH killifish.

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Hexabromocyclododecane and polychlorinated biphenyls increase resistance of hepatocellular carcinoma cells to cisplatin through the phosphatidylinositol 3-kinase/protein kinase B pathway

Cited by 25 publications

References 41 publications

Inhibition of DNM1L and mitochondrial fission attenuates inflammatory response in fibroblast‐like synoviocytes of rheumatoid arthritis

Inhibition of DNM1L and mitochondrial fission attenuates inflammatory response in fibroblast‐like synoviocytes of rheumatoid arthritis

Aroclor1254 disrupts the blood–testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway

Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA

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