Reduction of Intracellular Chloride Concentration Promotes Foam Cell Formation

Wu, Qianqian; Liu, Xiaoyun; Xiong, Li-Xiong; Shang, Jie; Mai, Xiao-Yi; Pang, Rui‐Ping; Su, Ying-Xue; Yu, Beixin; Yuan, Jiani; Yang, Chia-Han; Wang, Yanli; Zhou, Ping; Lv, Xiao‐Fei; Liu, Jie; Zhou, Jia‐Guo; Liang, Shi-Dong

doi:10.1253/circj.cj-15-1209

Cited by 22 publications

(23 citation statements)

References 26 publications

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“…Western blotting was performed as we previously described . Briefly, cells were washed twice with ice‐cold phosphate‐buffered saline and lysed with RIPA lysis buffer (Beyotime, Jiangsu, China) containing 1% protease inhibitor cocktail (Merck, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of Orai1‐mediated Ca²⁺ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil

Tang

Xia

et al. 2016

J Cellular Molecular Medi

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Increasing evidence supports that activation of store‐operated Ca2+ entry (SOCE) is implicated in the chemoresistance of cancer cells subjected to chemotherapy. However, the molecular mechanisms underlying chemoresistance are not well understood. In this study, we aim to investigate whether 5‐FU induces hepatocarcinoma cell death through regulating Ca2+‐dependent autophagy. [Ca2+]i was measured using fura2/AM dye. Protein expression was determined by Western blotting and immunohistochemistry. We found that 5‐fluorouracil (5‐FU) induced autophagic cell death in HepG2 hepatocarcinoma cells by inhibiting PI3K/AKT/mTOR pathway. Orai1 expression was obviously elevated in hepatocarcinoma tissues. 5‐FU treatment decreased SOCE and Orai1 expressions, but had no effects on Stim1 and TRPC1 expressions. Knockdown of Orai1 or pharmacological inhibition of SOCE enhanced 5‐FU‐induced inhibition of PI3K/AKT/mTOR pathway and potentiated 5‐FU‐activated autophagic cell death. On the contrary, ectopic overexpression of Orai1 antagonizes 5‐FU‐induced autophagy and cell death. Our findings provide convincing evidence to show that Orai1 expression is increased in hepatocarcinoma tissues. 5‐FU can induce autophagic cell death in HepG2 hepatocarcinoma cells through inhibition of SOCE via decreasing Orai1 expression. These findings suggest that Orai1 expression is a predictor of 5‐FU sensitivity for hepatocarcinoma treatment and blockade of Orai1‐mediated Ca2+ entry may be a promising strategy to sensitize hepatocarcinoma cells to 5‐FU treatment.

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Section: Methodsmentioning

confidence: 99%

“…Immunoprecipitation was performed as described previously . Cell lysates were immunoprecipitated with Stim1 antibody overnight at 4°C, followed by incubation with Protein A/G–Sepharose (Santa Cruz Biotechnology) for 4 hrs.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Orai1‐mediated Ca²⁺ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil

Tang

Xia

et al. 2016

J Cellular Molecular Medi

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“…In mammalian cells, Cl À modulates the G1/S cell-cycle checkpoint through p21 through the stress-activated protein kinases (MAPKs) p38, and JNK [Ohsawa et al, 2010;Shiozaki et al, 2011]. These kinases are also involved in foam cell formation under low intracellular chloride [Wu et al, 2016]. In addition, we have recently demonstrated that Cl À can act as a second messenger modulating the expression of several "chloridedependent" genes, including GLRX5 and RPS27 [Valdivieso et al, 2016], and several studies have shown Cl À effects in neurons, including the modulation of the expression of GABA A subunits [Succol et al, 2012].…”

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Intracellular Chloride Concentration Changes Modulate IL-1β Expression and Secretion in Human Bronchial Epithelial Cultured Cells

et al. 2017

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Cystic fibrosis (CF) is caused by mutations in the CFTR gene, which encodes a cAMP-regulated chloride channel. Several cellular functions are altered in CF cells. However, it is not clear how the CFTR failure induces those alterations. We have found previously several genes differentially expressed in CF cells, including c-Src, MUC1, MTND4, and CISD1 (CFTR-dependent genes). Recently, we also reported the existence of several chloride-dependent genes, among them GLRX5 and RPS27. Here, varying the intracellular chloride concentration [Cl ] of IB3-1 CF bronchial epithelial cells, we show that IL-1β mRNA expression and secretion are also under Cl modulation. The response to Cl is biphasic, with maximal effects at 75 mM Cl . The regulation of the IL-1β mRNA expression involves an IL-1β autocrine effect, since in the presence of the IL-1β receptor antagonist IL1RN or anti-IL-1β blocking antibody, the mRNA response to Cl disappeared. Similar effects were obtained with the JNK inhibitor SP600125, the c-Src inhibitor PP2 and the IKK inhibitor III (BMS-345541). On the other hand, the IL-1β secretion is still modulated by Cl in the presence of IL-1RN, IL-1β blocking antibody, or cycloheximide, suggesting that Cl is affecting the IL-1β maturation/secretion, which in turn starts an autocrine positive feedback loop. In conclusion, the Cl anion acts as a second messenger for CFTR, modulating the IL-1β maturation/secretion. The results also imply that, depending on its intracellular concentration, Cl could be a pro-inflammatory mediator. J. Cell. Biochem. 118: 2131-2140, 2017. © 2016 Wiley Periodicals, Inc.

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“…The responses to low [Cl -] i may be involved in many signaling pathways. Low Cl -medium promoted endothelial cell inflammation by activating the nuclear factor-κB pathway [9] , and foam cell formation by low Cl − medium was mediated by activation of JNK and the p38 mutagen-activated protein kinesis pathway [29] . Therefore, another possibility is that the signaling pathways involved in low [Cl -] i are various because of the cell type or tissue properties.…”

Section: Wwwchinapharcom Zhang Yj Et Almentioning

confidence: 99%

WNK1 is required for proliferation induced by hypotonic challenge in rat vascular smooth muscle cells

et al. 2017

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Hypotonic challenge evoked vascular cell proliferation through activation of volume-regulated ·H 2 0), which caused significantly increase in WNK1 phosphorylation without altering WNK1 protein expression. WNK1 overexpression significantly increased hypotonic-induced A10 cell proliferation, whereas silencing of WNK1 caused an opposite action. WNK1 mutation did not affect hypotonic-induced WNK1 phosphorylation and cell proliferation. Silencing of WNK1 caused cell cycle arrest at G 0 /G 1 phase and prevented transition from G 1 to S phase, whereas the WNK1 overexpression accelerated cell cycle transition from G 1 to S phase. Silencing of WNK1 significantly inhibited cyclin D1/cyclin E1 expression and increased p27KIP/p21CIP expression. WNK1 overexpression significantly increased cyclin D1/cyclin E1 expression and reduced p27 KIP /p21 CIP expression. In addition, WNK1 knockdown or overexpression significantly attenuated or increased the hypotonic-induced phosphorylation of Akt and PI3K respectively. In conclusion, the reduction in [Cl -] i caused by hypotonic challenge-induced VRCC opening evokes WNK1 phosphorylation in A10 VSMCs, which mediates cell cycle transition from G 0 /G 1 to S phase and proliferation through the PI3K-Akt signaling pathway.

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Reduction of Intracellular Chloride Concentration Promotes Foam Cell Formation

Cited by 22 publications

References 26 publications

Inhibition of Orai1‐mediated Ca²⁺ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil

Inhibition of Orai1‐mediated Ca²⁺ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil

Intracellular Chloride Concentration Changes Modulate IL-1β Expression and Secretion in Human Bronchial Epithelial Cultured Cells

WNK1 is required for proliferation induced by hypotonic challenge in rat vascular smooth muscle cells

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Reduction of Intracellular Chloride Concentration Promotes Foam Cell Formation

Cited by 22 publications

References 26 publications

Inhibition of Orai1‐mediated Ca2+ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil

Inhibition of Orai1‐mediated Ca2+ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil

Intracellular Chloride Concentration Changes Modulate IL-1β Expression and Secretion in Human Bronchial Epithelial Cultured Cells

WNK1 is required for proliferation induced by hypotonic challenge in rat vascular smooth muscle cells

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Inhibition of Orai1‐mediated Ca²⁺ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil

Inhibition of Orai1‐mediated Ca²⁺ entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5‐fluorouracil