INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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IF 4.784
Qiang Chu,Shuang Zhang,Lushuang Yu,Yonglu Li,Yangyang Liu,Xiang Ye,Xiaodong Zheng
The tubers of Apios americana Medikus possess high nutritional value and have been used as food in many countries for a long time. However, few researches have focused on the tuber polysaccharides. In the present study, a purified polysaccharide (ATP-1) was isolated with the average molecular weights of 12.16 kDa. ATP-1 significantly suppressed the release of nitric oxide (NO) and inflammatory cytokines from LPS-induced RAW 264.7 cells, as well as oxidative stress and mitochondrial dysfunction. Meanwhile, ATP-1 reduced oxidative damage via the NF-κB, MAPKs and Nrf2-Keap1 signaling pathways in RAW264.7 macrophages. Furthermore, autophagy was activated by HMGB1-Beclin1, Sirt1-FoxO1 and Akt-mTOR signaling pathways, leading to a relief of oxidative stress, mitochondrial dysfunction, inflammation and an expression enhancement of autophagy-related proteins, such as LC3, Beclin1, Atg4, Atg5, and Atg7. In summary, our results suggested that ATP-1 might help to activate the anti-inflammation system，resulting in prevention of LPS-induced damage in RAW264.7 cells.
研究领域:
药理学
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免疫学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2019
·
IF 3.775
Leying Jiang,Zhen Li,Yixi Xie,Liangliang Liu,Yi Cao
Recent studies suggest that phytochemicals , as part of the food matrix, might alter the toxicity of nanoparticles (NPs); however, relatively few studies have investigated the impact of anthocyanidins on the toxicity of NPs to cells lining the gastrointestinal tract. Therefore, this study used cyanidin chloride (CC) as the model for anthocyanidins and investigated the effects of CC on the toxicity of ZnO or Ag NPs to Caco-2 cells. Exposure to ZnO but not Ag NPs significantly induced cytotoxicity. The presence of CC, but not its analog quercetin (Qu), modestly protected Caco-2 cells from ZnO NP exposure. However, the intracellular superoxide, Zn ions , or release of interleukin-8 after ZnO NP exposure were not significantly affected by the presence of CC. Rather, CC promoted the expression of autophagic genes ATG5 , ATG7 , and BECN1 as well as the ratio of LC3-II/I after exposure to ZnO NPs. Meanwhile, the presence of autophagic inhibitors (chloroquine, NH 4 Cl, bafilomycin A1) significantly promoted the cytotoxicity of ZnO NPs and inhibited the cytoprotective effects of CC. In conclusion, these data suggest that CC could modestly protect Caco-2 cells from ZnO NP exposure, probably through the induction of autophagy.
研究领域:
毒理学
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细胞生物学
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药理学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
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IF 6.1
Yanzi Zhao,Yujing Niu,Xuefei Wang,Peng Wan,Zhanfei Ma,Jian Sun,Shoufang Jiang,Ling Xue,Nan Liu
Indium-tin oxide nanoparticles (Nano-ITO) are widely used in various applications as infrared shielding materials, which increase the risk of occupational exposure. According to reports, Nano-ITO can cause indium lung disease in occupational exposed workers, but the specific mechanism of Nano-ITO-induced pulmonary toxicity remains unclear. In this study, 50 8-week-old male Sprague-Dawley rats were divided into five groups (10 rats in each group) as follows: control group (physiological saline), 1.2 mg/kg Nano-ITO group, 6 mg/kg Nano-ITO group, N-Acetyl-L-Cysteine (NAC) control group (200 mg/kg), and NAC + Nano-ITO group (200 mg/kg NAC intraperitoneal injection, after 1.5 h, 6 mg/kg Nano-ITO intratracheal instillation), twice a week for 12 weeks. Pathological and ultrastructural changes in the rat lung tissue, immunofluorescence assays, immunohistochemistry, protein and mRNA levels of apoptosis- and autophagy-related genes were measured. The levels of ROS, MDA, H 2 O 2 , and LDH, and the activities of T-AOC and SOD, were determined using oxidative stress assay kits. The results showed that Nano-ITO caused strong pulmonary inflammation, pulmonary alveolar proteinosis, and pulmonary interstitial fibrosis. In addition, Nano-ITO-induced oxidative stress in rat lungs presented as increased levels of ROS and H 2 O 2 in the lungs, increased LDH and MDA levels, SOD and T-AOC activity in BALF, and activation of the Nrf2/NQO1/HO-1 signaling pathway. Intriguingly, Nano-ITO significantly increased the protein expression of microtubule-associated protein light chain 3 (LC3-II), the protein levels of autophagy-related genes 5 (ATG5), and Beclin-1 (BECN1), and reduced the protein levels of phosphatidylinositol 3-kinase (PI3K) in lung tissues. In addition, transmission electron microscopy (TEM) showed a significant increase in autophagic vesicles in the cytoplasm of lungs treated with Nano-ITO, indicating that Nano-ITO induces autophagy in rat lungs. Moreover, apoptosis also participates in Nano-ITO-induced pulmonary injury in a synchronous manner, as evidenced by the enhancement of TUNEL-positive signals and activation of the apoptosis pathway (Bax and Bcl-2 positive proportions). NAC supplementation restored most of the pathological structural features of rat lung tissue to their physiological range and effectively weakened apoptosis, as demonstrated by the notable reductions in TUNEL, Bax, and Bcl-2 protein expression levels in the lungs. Although autophagy was detected in the lungs of rats in the Nano-ITO and NAC + Nano-ITO groups, we discovered that NAC could rescue the expression of ATG5 and BECN1 induced by Nano-ITO, thus indicating that exposure to Nano-ITO promotes pulmonary apoptosis and autophagy by mediating oxidative stress. These results indicate that Nano-ITO can cause pulmonary injury by inducing oxidative stress, which activates apoptosis and autophagy, ultimately leading to alveolar proteinosis and interstitial fibrosis.
研究领域:
毒理学
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纳米技术
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呼吸医学
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分子生物学
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药理学
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病理学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Minghui Cai,Qiuyuan Li,Yang Cao,Yujia Huang,Haixu Yao,Chen Zhao,Jiao Wang,Hui Zhu
Autophagy is closely related to the aging of various organ systems, including ovaries. Quercetin has a variety of biological activities , including potential regulation of autophagy. However, whether quercetin-regulated autophagy activity affects the process of ovarian aging and injury has not been clarified yet. This study explores whether quercetin can resist H 2 O 2 -induced aging and injury of granulosa cells by regulating autophagy and its related molecular mechanisms in vitro experiments. The cell viability , endocrine function, cell aging , and apoptosis were detected to evaluate the effects of quercetin and autophagy regulators like 3-methyladenine and rapamycin . The levels of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 were determined by Western blot to assess the effects of quercetin, 3-methyladenine and rapamycin on autophagy. Our results showed quercetin resisted H 2 O 2 -induced granulosa cell aging and injury by activating protective autophagy. The treatment of 3-methyladenine and rapamycin confirmed the protective function of autophagy in H 2 O 2 -induced granulosa cells. 3-methyladenine treatment inhibited the expression of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 and abolished the positive effects on cell viability , estradiol secretion, and cell apoptosis activated by quercetin. In conclusion, quercetin activates autophagy by upregulating the expression of autophagy-related proteins to resist H 2 O 2 -induced aging and injury, which is crucial for stabilizing the function of granulosa cells under oxidative injury conditions and delaying aging. This study may explain the protective effects of quercetin on ovarian aging and injury from the perspective of regulating autophagy.
研究领域:
生殖生物学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Caiying Zhang,Zhisheng Hu,Ruiming Hu,Shaoxing Pi,Zejing Wei,Chang Wang,Fan Yang,Chenghong Xing,Gaohui Nie,Guoliang Hu
Pyroptosis and autophagy are two different biological processes that determine cell fates. Our previous studies revealed that pyroptosis and autophagy were involved in cytotoxicity co-induced by molybdenum (Mo) and cadmium (Cd) in duck renal tubular epithelial cells, but crosstalk between them is unclear. Hence, the cells were treated with 500.0 μM Mo, 4.0 μM Cd, 10.0 μM Z-YVAD-fluoromethylketone (YVAD), 2.5 μM 3-methyladenine (3-MA) and 10.0 μM chloroquine (CQ) alone or in combination for 12 h (CQ for the last 4 h). Under Mo and Cd co-stress, data evidenced that YVAD addition decreased the number of autophagosomes, LC3 puncta, and AMPKα-1, Atg5, Beclin-1, LC3A, LC3B mRNA levels and LC3-II/LC3-I, Beclin-1 protein levels, and increased p62 expression levels. Besides, both 3-MA and CQ addition increased NLRP3, Caspase-1, NEK7, ASC, GSDMA, GSDME, IL-1β, IL-18 mRNA levels, NLRP3, Caspase-1 p20, ASC, GSDMD protein and ROS levels, and NO, LDH, IL-1β, IL-18 releases. Collectively, our results revealed that pyroptosis and autophagy co-induced by Mo and Cd were interrelated in duck renal tubular epithelial cells, and inhibiting pyroptosis might attenuate Mo and Cd co-induced autophagy, but inhibiting autophagy might promote Mo and Cd co-induced pyroptosis.
研究领域:
细胞生物学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
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2020
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IF 5.715
Jun Zhu,Lei Tang,Shanlei Qiao,Lijuan Wang,Yiming Feng,Li Wang,Qian Wu,Ping Ding,Zhan Zhang,Lei Li
Methylmercury (MeHg) is a ubiquitous environmental toxicant with neurotoxic effects. Although its neurotoxicity had been more studied, the role of gut microbiota remains unclear. In this study, adult zebrafish and larvae were exposed to MeHgCl at the dose of 0, 1 and 10 ng/mL. MeHgCl exposure impaired the locomotor activity via upregulation of apoptosis and autophagy related genes in the brain. Intestinal and cerebral metabolome indicated that phosphatidylinositol signaling system and inositol phosphate metabolism pathways were significantly impacted in adult zebrafish upon MeHgCl exposure. The levels of myo-inositol (MI) in the intestine and brain were decreased and positively correlated. 16 S rRNA sequencing data from adult zebrafish showed that MeHgCl exposure also shifted the structure of gut microbiota and reduced the relative abundance of Bacteroidetes and Proteobacteria , which were further identified at genus level as Aeromonas and Cetobacterium . Further functional analysis indicated that MeHgCl disrupted inositol phosphate metabolism of gut microbiota. Notably, MI supplementation restored the impairment of locomotor activity and inhibited the upregulation of apoptosis and autophagy related genes, such as bcl-2 and atg5 . Thus, this study not only revealed the key role of gut microbiota in MeHgCl-mediated neurotoxicity but also gave new insights into antagonizing its toxicity.
研究领域:
毒理学
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神经科学
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2018
·Vol. 9
·期 12
·6349-6359
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IF 3.289
Ying Chen,Jianjun Chen,Xiaoxue Sun,Xiaoxiao Shi,Lei Wang,Liyong Huang,Wenke Zhou
(−)-Epigallocatechin-3-gallate (EGCG), the main bioactive component of tea catechins, exhibits broad-spectrum health efficacy against mitochondrial damage after subarachnoid hemorrhage (SAH). The mechanisms, however, are largely unknown. Here, the ability of EGCG to rescue mitochondrial dysfunction and mitochondrial dynamics following the inhibition of cell death was investigated by using in vitro and in vivo SAH models. EGCG blocked the cytosolic channel ([Ca2+])i influx via voltage-gated calcium channels (VGCCs), which induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) release. As expected, EGCG ameliorated oxyhemoglobin (OxyHb)-induced impairment of mitochondrial dynamics by regulating the expression of Drp1, Fis1, OPA1, Mfn1, and Mfn2. As a result, EGCG restored the increases in fragmented mitochondria and the mtDNA copy number in the OxyHb group to almost the normal level after SAH. In addition, the normal autophagic flux induced by EGCG at both the initiation and formation stages regulated Atg5 and Beclin-1 after SAH for the timely elimination of damaged mitochondria. In the end, EGCG increased the neurological score by decreasing cell death through the cyt c-mediated intrinsic apoptotic pathway. The results revealed the mechanisms behind the neuroprotective effects of EGCG via inhibition of the overloaded [Ca2+]i-induced mitochondrial dysfunction and the imbalanced mitochondrial fusion and fission cycle. Therefore, the simultaneous inhibition and timely elimination of damaged mitochondria could determine the therapeutic effect of EGCG.
研究领域:
神经保护
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线粒体生物学
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神经病学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Shiqi Zhu,Haimei Wen,Wenling Wang,Yong Chen,Fengmei Han,Wentao Cai
Ethnopharmacological relevance Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, Danshen in Chinese), a traditional Chinese medicine , has been clinically used to prevent and treat various diseases, such as cardiovascular and cerebrovascular diseases , diabetes, and hepatitis B, in China and some other Asian countries. Lithospermic acid (LA), a polyphenol derived from S . miltiorrhiza , has been reported to exhibit multiple pharmacological properties, such as anti-inflammatory, anti-HIV, and anti-carbon tetrachloride-induced liver injury activities. However, little is known about the anti-hepatitis B virus (HBV) activity of LA. Aim of the study The study was projected to investigate the anti-HBV activity of LA in vitro (HepG2.2.15 and pHBV1.3-transfected HepG2 cells) and in vivo (pAAV-HBV1.2 hydrodynamic injection [HBV-HDI] mice) and explore the potential mechanism as well. Materials and methods Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) contents were detected by ELISA kits. HBV DNA and hepatitis B core antigen (HBcAg) levels were evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry assay, respectively. The proteins in autophagy process, lysosomal acidic function, and autophagy-related signaling pathways were examined by Western blot . Transmission electron microscopy was used to observe the number of autophagosomes and autolysosomes. Confocal microscopy was applied to analyze the autophagic flux and lysosomal acidification, using mCherry-enhanced green fluorescent protein (EGFP)-microtubule-associated protein light chain (LC)3 and lysosomal probes, respectively. Results LA exhibited anti-HBV activity by inhibiting HBV DNA replication in HepG2.2.15 and pHBV-transfected HepG2 cells in dose- and time-dependent manners and hampering HBsAg and HBeAg levels in HepG2.2.15 cells to a certain extent. LA reduced HBV DNA, HBsAg/HBeAg, and HBcAg levels in the serum/liver tissues of HBV-HDI C57BL/6 mice during the 3-week treatment and suppressed the withdrawal rebound of HBV DNA and HBsAg in the mice serum. LA increased LC3-II protein expression and the number of autolysosomes/autophagosomes and promoted the degradation of sequestosome 1(p62) protein in vitro and in vivo . LA enhanced the co-localization of LC3 protein with autolysosomes, further confirming the ability of LA to induce a complete autophagy. Knockdown of autophagy-related gene (Atg) 7 or 5 in vitro and administration of 3-methyladenine (an autophagic inhibitor) in vivo disabled the inhibitory efficacy of LA on HBV DNA replication, suggesting that the anti-HBV efficacy of LA depended on its ability of inducing autophagy. LA could enhance lysosomal acidification and improve the function of lysosomes by promoting the protein expression of lysosomal-associated membrane protein (LAMP)-1, LAMP-2, and mature cathepsin D , which may contribute to the autophagic induction of LA. LA inhibited the activation of AKT and mammalian target of rapamycin (mTOR) induced by HBV, which was reversed by IGF-1 (an agonist of the PI3K/AKT/mTOR signaling pathway), indicating that LA elicited autophagy through hampering the PI3K/AKT/mTOR signaling pathway. Conclusion We revealed the anti-HBV activity and mechanism of LA in vitro and in vivo . This study facilitates a new understanding of the anti-HBV potent components of S. miltiorrhiza and sheds light on LA for further development as an active constituent or candidate used in the therapy against HBV infection.
研究领域:
药理学
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病毒学
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分子生物学
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中医药
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产品关联
DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
·
2021
·
IF 5.246
Zhang Yin,Wang Qinge,Xu Yuping,Sun Jing,Ding Yanbo,Wang Li,Chen Bingfang,Sun Kewen,Chen Jianping
Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）