INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Wenqian Yu,Jialin Liu,Chang Yang,Yao Luo,Hailin Mu,Shuo Wang,Wei Dong,Meie Jia,Zhipeng Dong,Xinpei Lu,Jiawei Wang
Periodontitis is a microbe-driven infectious disease, in which Porphyromonas gingivalis (Pg) plays a keystone role. As the front line to eliminate dysbiotic microbiota, macrophages are critical for recognition, phagocytosis and digestion of bacteria. However, deficiencies in the antimicrobial function of periodontal macrophages lead to diminished Pg clearance and destructive periodontal inflammation. Cold atmospheric plasma (CAP) enables non-invasive treatment by producing reactive species including reactive oxygen species (ROS), reactive nitrogen species (RNS) and electro-magnetic field, and is of great interest for infectious diseases. These radicals have a significant influence on cellular biochemistry and are crucial components of the immune system. The CAP jet using helium gas was developed and driven by the bipolar pulse high voltage. The negative voltage was 5 kV and the positive voltage was 10 kV. The irradiation time was set to 120 s for in vivo experiments and 80 s for in vitro experiments. In vivo experiments demonstrated that CAP significantly alleviated periodontitis. In addition to the directly antimicrobial effects, in vitro experiments demonstrated that CAP enhanced intracellular killing of Pg by bone marrow-derived macrophages (BMMs) and murine macrophage cell line RAW 264.7 in a ROS-dependent manner. BMMs were collected from the tibias and femurs of healthy C57BL/6 mice aged 6–8 weeks old. Mechanistically, it is found that CAP promotes microtubule-associated protein 1A/1B-light chain 3 (MAP1LC3, LC3)-associated phagocytosis (LAP) in macrophages to defend against Pg. Therefore, CAP is proposed a potential therapy for effectively alleviating periodontitis through regulating the bactericidal activity of macrophages.
研究领域:
口腔医学
·
免疫学
·
微生物学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Guanghua Sun,Yahua Zeng,Fu Luo,Lixian Zhang,Jinqu Tan,Jie Tong,Lu Yang,Danni Liu,Liu Liu,Jun Zhou
Our study aimed to investigate the effect of electroacupuncture pretreatment on the inflammatory response and expression levels of LC3-II/I and Beclin 1 using a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Eighteen male Sprague-Dawley (SD) rats were randomly divided into three groups: normal control group (NC, n = 6), LSP modeling group (LM, n = 6), and electroacupuncture group (EA, n = 6). Rats in the EA group received electroacupuncture pretreatment at bilateral Zusanli (ST36) and Chize (LU5) points for five days (30 min each time daily, frequency; 3 Hz/15 Hz, intensity; 1 mA). Rats in the EA and LM groups were then injected with 5 mg/kg LPS (Beijing, Solarbio Company, concentration; 5 mg/mL) through the tail vein, while those in the NC group were injected with 5 mg/kg saline. The animals were sacrificed six hours after LPS or saline injection through cervical vertebrae by dislocation under deep anesthesia. Orbital blood was collected for the analysis of serum inflammatory factors including interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β). The lower left lung was excised, stained with hematoxylin-eosin (HE), and subjected to histopathological analysis. The mRNA and protein expression of Beclin 1 and LC3 II/I in the lower right lung tissues were detected via RT-qPCR and Western blot analyses, respectively. The results showed that lung injury score was significantly higher in the LM group than that of the NC group () and EA group (). The IL-1β contents were significantly decreased in the EA group () than in the LM group. In contrast, the GF-β contents were increased in the EA group significantly when compared with the LM group (). RT-qPCR and Western blot detection showed that the relative gene expression of LC3‐II/I and Beclin 1 was significantly lower in the EA group than in the LM group (). However, the relative protein expression level of LC3‐II/I and Beclin 1 was slightly lower in the EA group than the in LM group (). These results show that electroacupuncture pretreatment reduces the inflammatory response in ALI and can protect lung tissue by inhibiting the gene and protein expression levels of LC3‐II/I and Beclin 1.
研究领域:
药理学
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免疫学
·
肺病学
·
中医
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 8
·e2988
·
IF 5.965
Yan Siyuan,Liu Ling,Ren Fengxia,Gao Quan,Xu Shanshan,Hou Bolin,Wang Yange,Jiang Xuejun,Che Yongsheng
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ -H2AX, a marker for the DNA double-strand breaks (DSB). Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, was found to enhance the autophagic flux concurring with increase in the frequency of micronuclei accrued upon inhibition of autophagy, and similar results were also obtained in the rasfonin-treated cells. Moreover, the punctate LC3 staining colocalized with micronuclei. Unexpectedly, deprivation of SQSTM1/p62 alone accumulated micronuclei, which was not further increased upon challenge with ST. Rad51 is a protein central to repairing DSB by homologous recombination and treatment with ST or rasfonin decreased its expression. In several cell lines, p62 appeared in the immunoprecipites of Rad51, whereas LC3, Ulk1 and p62 interacted with PARP-1, another protein involved in DNA repair and genomic stability. In addition, knockdown of either Rad51 or PARP-1 completely inhibited the ST-induced autophagic flux. Taken together, the data presented here demonstrated that both LC3-II and the phosphorylated Ulk1 localized in nuclei and interacted with the proteins essential for nuclear stability, thereby revealing a more intimate relationship between autophagy and genomic stability.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
·
药理学
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DOI
PubMed
高影响因子
Autophagy
·
2026
·
IF 18.6
Jiabin Wang,Junkai Wang,Xinyu Xiao,Lingling Zheng,Xia Lu,Li Wang,Xin Bian,Long Lin
Cells dynamically regulate membrane protein delivery to meet physiological demands, yet how external cues rapidly mobilize unconventional Golgi-bypass exocytic routes in vivo remains unclear. Here we define LC3/Atg8-associated carrier exocytosis (LACES), a conserved program that couples microbial cues to accelerated surface delivery. In the Caenorhabditis elegans intestine, phenazine-1-carboxamide (PCN) triggers VPS-34-dependent PtdIns3P generation at ILE-1/ERGIC-53 subdomains, enabling Atg8ylation on preexisting single-membrane RAB-8 carriers. This route accelerates delivery of the ABC transporter PGP-1 and improves host survival during infection, while operating independently of the unfolded protein response, canonical macroautophagy/autophagy initiation modules, and LC3-associated phagocytosis regulators. The pathway is engaged by multiple extracellular bacteria and also functions in mammalian epithelia, where PCN increases apical ΔF508-CFTR delivery in polarized Caco-2 cysts with measurable functional improvement and enhances LC3-RAB8 interactions in mouse intestinal epithelium. These findings establish a conserved LC3-linked Golgi-bypass route and illustrate how microbial cues can rapidly rewire epithelial membrane trafficking to fortify barrier defense.Abbreviations: ABC: ATP-binding cassette; BFA: brefeldin A; CFTR: CF transmembrane conductance regulator; ERGIC: ER-Golgi intermediate compartment; FRAP: fluorescence recovery after photobleaching; LACES: LC3/Atg8-Associated Carrier Exocytosis; LAP: LC3-associated phagocytosis; PCA: phenazine-1-carboxylic acid; PCN: phenazine-1-carboxamide; PYO: pyocyanin; 1-HP: 1-hydroxyphenazine; ROS: reactive oxygen species; UPR: unfolded protein response
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产品关联
DOI
PubMed
高影响因子
Autophagy
·
2023
·
IF 13.3
Ligang Mei,Xiaorong Chen,Fujing Wei,Xue Huang,Lu Liu,Jia Yao,Jing Chen,Xunguang Luo,Zhuolin Wang,Aimin Yang
Proteolysis-targeting chimeras (PROTACs) based on the ubiquitin-proteasome system have made great progress in the field of drug discovery. There is mounting evidence that the accumulation of aggregation-prone proteins or malfunctioning organelles is associated with the occurrence of various age-related neurodegenerative disorders and cancers. However, PROTACs are inefficient for the degradation of such large targets due to the narrow entrance channel of the proteasome. Macroautophagy (hereafter referred to as autophagy) is known as a self-degradative process involved in the degradation of bulk cytoplasmic components or specific cargoes that are sequestered into autophagosomes. In the present study, we report the development of a generalizable strategy for the targeted degradation of large targets. Our results suggested that tethering large target models to phagophore-associated ATG16L1 or LC3 induced targeted autophagic degradation of the large target models. Furthermore, we successfully applied this autophagy-targeting degradation strategy to the targeted degradation of HTT65Q aggregates and mitochondria. Specifically, chimeras consisting of polyQ-binding peptide 1 (QBP) and ATG16L1-binding peptide (ABP) or LC3-interacting region (LIR) induced targeted autophagic degradation of pathogenic HTT65Q aggregates; and the chimeras consisting of mitochondria-targeting sequence (MTS) and ABP or LIR promoted targeted autophagic degradation of dysfunctional mitochondria, hence ameliorating mitochondrial dysfunction in a Parkinson disease cell model and protecting cells from apoptosis induced by the mitochondrial stress agent FCCP. Therefore, this study provides a new strategy for the selective proteolysis of large targets and enrich the toolkit for autophagy-targeting degradation.Abbreviations: ABP: ATG16L1-binding peptide; ATG16L1: autophagy related 16 like 1; ATTEC: autophagy-tethering compound; AUTAC: autophagy-targeting chimera; AUTOTAC: autophagy-targeting chimera; Baf A1: bafilomycin A1; BCL2: BCL2 apoptosis regulator; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CASP3: caspase 3; CPP: cell-penetrating peptide; CQ: chloroquine phosphate; DAPI: 4’,6-diamidino-2-phenylindole; DCM: dichloromethane; DMF: N,N-dimethylformamide; DMSO: dimethyl sulfoxide; EBSS: Earle′s balanced salt solution; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; FITC: fluorescein-5-isothiocyanate; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HEK293: human embryonic kidney 293; HEK293T: human embryonic kidney 293T; HPLC: high-performance liquid chromatography; HRP: horseradish peroxidase; HTT: huntingtin; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFF: mitochondrial fission factor; MTS: mitochondria-targeting sequence; NBR1: NBR1 autophagy cargo receptor; NLRX1: NLR family member X1; OPTN: optineurin; P2A: self-cleaving 2A peptide; PB1: Phox and Bem1p; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; PROTACs: proteolysis-targeting chimeras; QBP: polyQ-binding peptide 1; SBP: streptavidin-binding peptide; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SPATA33: spermatogenesis associated 33; TIMM23: translocase of inner mitochondrial membrane 23; TMEM59: transmembrane protein 59; TOMM20: translocase of outer mitochondrial membrane 20; UBA: ubiquitin-associated; WT: wild type.
研究领域:
神经退行性疾病
·
癌症
·
药物发现
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2019
·Vol. 9
·期 1
·1-13
·
IF 4.011
Hou Bolin,Wang Gang,Gao Quan,Wei Yanjie,Zhang Caining,Wang Yange,Huo Yuqing,Yang Huaiyi,Jiang Xuejun,Xi Zhijun
Sunitinib (ST), a multitargeted receptor tyrosine kinase inhibitor, has been demonstrated to be effective for the treatment of renal carcinoma. It has been reported that ST is involved in the mediation of autophagy; however, its regulatory role in the autophagic process remains controversial. Furthermore, the mechanism by which activated AMP-activated protein kinase (AMPK) negatively regulates autophagy remains nearly unexplored. In the present study, we revealed that ST inhibited AMPK activity and regulated autophagy in a cell type- and dose-dependent manner. In a number of cell lines, ST was demonstrated to inhibit H 2 O 2 -induced autophagy and the phosphorylation of acetyl-CoA carboxylase (ACC), whereas alone it could block the autophagic flux concurrent with increased expression of p62. An immunoprecipitation assay revealed that LC3 directly interacted with p62, whereas ST increased punctate LC3 staining, which was well colocalized with p62. Taken together, we reveal a previously unnoticed pathway for ST to regulate the autophagic process, and p62, although often utilized as a substrate in autophagy, plays a critical role in regulating the inhibition of ST in both basal and induced autophagy.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Sun Yueshan,Jiang Xueqin,Pan Rong,Zhou Xiaogang,Qin Dalian,Xiong Rui,Wang Yiling,Qiu Wenqiao,Wu Anguo,Wu Jianming
The pathogenesis of Huntington’s disease (HD), an inherited progressive neurodegenerative disease, is highly associated with the cytotoxicity-inducing mutant huntingtin (mHtt) protein. Emerging evidence indicates that autophagy plays a pivotal role in degrading aggregated proteins such as mHtt to enhance neuronal viability. In this study, by employing preparative high-performance liquid chromatography (pre-HPLC), ultra-high performance liquid chromatography diode-array-detector quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q-TOF-MS) and nuclear magnetic resonance (NMR), three escins, escin IA (EA), escin IB (EB) and isoescin IA (IEA), were isolated and identified from the seed of Aesculus chinensis Bge. (ACB). After EGFP-HTT74-overexpressing HT22 cells were treated with EA, EB and IEA at safe concentrations, the clearance of mHtt and mHtt-induced apoptosis were investigated by Western blot, immunofluorescence microscopy and flow cytometry methods. In addition, the autophagy induced by these escins in HT22 cells was monitored by detecting GFP-LC3 puncta, P62 and LC3 protein expression. The results showed that EA, EB and IEA could significantly decrease mHtt levels and inhibit its induced apoptosis in HT22 cells. In addition, these three saponins induced autophagic flux by increasing the ratio of RFP-LC3 to GFP-LC3, and by decreasing P62 expression. Among the tested escins, EB displayed the best autophagy induction, which was regulated via both the mTOR and ERK signaling pathways. Furthermore, the degradation of mHtt and the commensurate decrease in its cytotoxic effects by EA, EB and IEA were demonstrated to be closely associated with autophagy induction, which depended on ATG7. In conclusion, we are the first to report that the escins, including EA, EB and IEA are novel autophagy inducers that degrade mHtt and inhibit mHtt-induced apoptosis in vitro and in vivo. As a result of these findings, the triterpenoid saponins in ACB might be considered to be promising candidates for the treatment of HD in the future.
研究领域:
神经科学
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药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2021
·Vol. 25
·期 11
·4962-4973
·
IF 5.31
Mingyu He,Gege Yan,Yang Wang,Rui Gong,Hong Lei,Shuting Yu,Xiaoqi He,Guanghui Li,Weijie Du,Tianshuai Ma,Manqi Gao,Meixi Yu,Shenzhen Liu,Zihang Xu,Elina Idiiatullina,Naufal Zagidullin,Valentin Pavlov,Benzhi Cai,Ye Yuan,Lei Yang
Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
·
光生物学
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产品关联
DOI
PubMed
高影响因子
FEBS Journal
·
2025
·
IF 4.2
Yuqing Shen,Yi Shen,Xuru Wang,Fuhua Wang,Piaopiao Liu,Chen Sun,Ying Zhang,Feng-qin Miao,Jianqiong Zhang,Lixin Wang
Tight junctions (TJs) between pulmonary vascular endothelial cells (ECs) constitute the physical barrier that impedes the metastasis of tumor cells. We previously reported that circulating microtubule-associated proteins 1A/1B light chain 3B (LC3)-positive extracellular vesicles (LC3 + EVs) derived from primary breast tumors were essential for establishing the premetastatic niche. However, the roles of LC3 + EVs in inducing vascular permeability and promoting tumor metastasis are unclear. In this study, we revealed that the expression of occludin and tight junction protein 1 [also known as zona occludens protein 1 (ZO-1)], two major TJ proteins, could be reduced by circulating LC3 + EVs, which subsequently increased vascular permeability, facilitated the invasion of circulating tumor cells, and eventually resulted in increased lung metastasis. Heat shock protein 60 (HSP60) was identified as the key molecule on LC3 + EVs that induced the reduction of occludin and ZO-1 through the Toll-like receptor 2 (TLR2)–myeloid differentiation primary response protein MyD88 (MYD88)–Snail Family Transcriptional Repressor 1 (Snai1) signal cascade. Combined with our previous findings, these results demonstrate that removing circulating LC3 + EVs or targeting HSP60 on LC3 + EVs might be a promising way to prevent breast cancer lung metastasis.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
·
癌症转移
·
细胞外囊泡
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR CELL
·
2023
·
IF 16
Xue Huang,Jia Yao,Lu Liu,Jing Chen,Ligang Mei,Jingjing Huangfu,Dong Luo,Xinyi Wang,Changhai Lin,Xiaorong Chen,Yi Yang,Sheng Ouyang,Fujing Wei,Zhuolin Wang,Shaolin Zhang,Tingxiu Xiang,Dante Neculai,Qiming Sun,Eryan Kong,Edward W. Tate,Aimin Yang
p62 is a well-characterized autophagy receptor that recognizes and sequesters specific cargoes into autophagosomes for degradation. p62 promotes the assembly and removal of ubiquitinated proteins by forming p62-liquid droplets. However, it remains unclear how autophagosomes efficiently sequester p62 droplets. Herein, we report that p62 undergoes reversible S -acylation in multiple human-, rat-, and mouse-derived cell lines, catalyzed by zinc-finger Asp-His-His-Cys S -acyltransferase 19 (ZDHHC19) and deacylated by acyl protein thioesterase 1 (APT1). S -acylation of p62 enhances the affinity of p62 for microtubule-associated protein 1 light chain 3 (LC3)-positive membranes and promotes autophagic membrane localization of p62 droplets, thereby leading to the production of small LC3-positive p62 droplets and efficient autophagic degradation of p62-cargo complexes. Specifically, increasing p62 acylation by upregulating ZDHHC19 or by genetic knockout of APT1 accelerates p62 degradation and p62-mediated autophagic clearance of ubiquitinated proteins. Thus, the protein S -acylation-deacylation cycle regulates p62 droplet recruitment to the autophagic membrane and selective autophagic flux, thereby contributing to the control of selective autophagic clearance of ubiquitinated proteins.
研究领域:
细胞生物学
·
分子生物学
·
自噬
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2025
·
IF 2.8
Mengmeng Gao,Hao Ling,Chengxiang Guo,Yinan Hu,Jing Zhu,Jicang Wang
Cadmium, a bluish-white metallic, possesses a prolonged half-life in organisms, causing damage to multiple tissues and organs. Naringenin, a natural flavonoid antioxidant, mitigates cadmium-induced damage in organisms. However, the mechanism by which naringenin attenuates Cd-associated hepatocellular damage has not been fully elucidated. The present investigation consequently aimed to elucidate the mechanistic involvement of autophagy in cadmium hepatotoxicity using the rat model, with parallel assessment of naringenin's hepatoprotective efficacy. In this experiment, 24 SD rats underwent randomization to four experimental groups: (1) control (intraperitoneal saline injection), (2) Cd (1 mg/kg b.w. CdCl₂ intraperitoneal injection), (3) Cd + Nar (1 mg/kg b.w. CdCl₂ injection + 50 mg/kg b.w. naringenin oral gavage), and (4) Nar (50 mg/kg b.w. naringenin oral gavage) groups. After the 14-day interventions, serum and liver tissues were collected post-euthanasia. Hepatic injury markers (AST and ALT) and antioxidant enzymes (CAT and SOD) were quantified. Histopathology utilized HE and TUNEL staining. RT-qPCR and western blot analyses determined mRNA and protein expression levels of autophagy-related factors (p62 and LC3) and apoptosis-related factor (Caspase-3). The results demonstrated that cadmium exposure significantly reduced body weight, increased relative liver weight, elevated serum AST/ALT levels, and diminished hepatic CAT/SOD activity. Cadmium significantly upregulated both mRNA and protein expression levels of p62 and Caspase-3 while suppressing LC3 expression. Naringenin co-administration attenuated cadmium-induced hepatic injury, oxidative stress, impaired autophagy, and enhanced apoptosis. These findings collectively demonstrate that cadmium exposure induces hepatic injury and oxidative stress in rats through autophagy inhibition and apoptotic activation, while naringenin exerts protective effects by modulating these pathological processes.
研究领域:
毒理学
·
药理学
·
细胞生物学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2018
·
IF 3.974
Peng Chen,Na Geng,Dong Zhou,Yiran Zhu,Yuliang Xu,Kangping Liu,Yongxia Liu,Jianzhu Liu
Hexavalent chromium (Cr(VI)) is a common environmental pollutant. Exposure of Cr(VI) can lead to cell autophagy, but the preventive measures for diminishing Cr(VI)-induced autophagy need further study. COX-2 can be induced by several heavy metals and can lead to endoplasmic reticulum (ER) stress and autophagy; thus, COX-2, ER stress, and autophagy may be related. This study mainly investigated the role of COX-2 in the eIF2α-ATF4 pathway, which is a major pathway in cell autophagy. In this study, Cr(VI) was used as a xenobiotic to determine changes in the parameters of ER stress, autophagy, and COX-2 levels. At the same time, a clear contrast was obtained by assigning positive and negative controls of ER stress and autophagy. The results showed that during Cr(VI) invasion, the parameters of ER stress and autophagy (such as BiP, PERK, p62, LC3-II, and mTOR) were enhanced, similarly to the positive control of ER stress and/or the autophagy controls. Such enhancement is a protective mechanism for cell survival. Additionally, the COX-2 levels increased. Moreover, when COX-2 was inhibited, the PERK level remained high, whereas the LC3-II level decreased. This finding suggests that COX-2 specifically affects the interaction between ER stress and autophagy. Notably, this study reveals that Cr(VI) can induce ER stress and autophagy in DF-1 cells and that COX-2 plays an essential role in the interaction between ER stress and autophagy.
研究领域:
毒理学
·
细胞生物学
·
环境科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）