JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2021
·Vol. 25
·期 7
·3361-3370
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IF 5.31
Zheng Chen,Jianguo Zhang,Chenyang Dong,Dongsheng Li,Yuehan Yin,Wenhai Yu,Yuezhi Chen
In this study, the purpose of this study was to investigate the role of TNFAIP8 in gastric cancer (GC). The expression of TNFAIP8 was detected by RT-PCR or western blot . TNFAIP8 was silenced or overexpressed in two cell lines. CCK-8 assay, transwell assay and flow cytometry were used to analyse cell viability, cell invasion capability and apoptosis, respectively. Nude mice were inoculated with TNFAIP8 silencing or overexpressing cells to form transplanted tumours. HE staining and immunohistochemistry assay were performed to assess histopathological changes in tumours. We found that the mRNA and protein expression of TNFAIP8 were significantly up-regulated in GC tumour tissues and cells compared with the normal counterparts. Overexpression of TNFAIP8 in GC cells increased cell viability, decreased apoptosis and promoted the cell migration ability. Meanwhile, increased expression of TNFAIP8 promoted autophagy, while inhibiting mTOR-Akt-ULK1 signal pathway. In conclusions, this study presents data that TNFAIP8 inhibits GC cells presumably by down-regulating mTOR-Akt-ULK1 signal pathway and activating autophagy signal.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
CONNECTIVE TISSUE RESEARCH
·
2025
·
IF 2.1
Lin Liu,Zhuangzhuang Chu,Xiao Han,Jin Wu,Kunzhan Cai,Jiaohong Wang,Zixiang Guo,Shan Gao,Guoqing Li,Chunbo Tang
Objective We aimed to demonstrate the effects of creatine (Cr) on osteogenic differentiation (OD) in HDPSCs.Materials and methods HDPSCs were treated with Cr and an inhibitor of Cr transporter. The OD capacity was evaluated by detecting ALP staining and activity, alizarin red staining (ARS), as well as osteogenesis-related protein levels. Transcriptomic sequencing, western blotting, transmission electron microscopy, immunofluorescence staining, and autophagy-related protein marker detection were applied to illustrate the underlying mechanism. Furthermore, the impact of Cr on bone regeneration was investigated in vivo.Results We found that 1 mm of Cr effectively enhanced the OD of HDPSCs. The creatine group displayed significantly increased AMPK phosphorylation, overexpressed autophagy-related proteins, enhanced OD, and mineralization capabilities. We also found that ULK1 is the downstream molecule through which AMPK induces cellular autophagy. In vivo results demonstrated that Cr could increase the new bone formation of periodontitis.Conclusion Our research discovered a new AMPK-ULK1-autophagy pathway through which Cr enhances OD in HDPSCs. Cr enhanced HDPSCs-mediated periodontal tissue regeneration in a periodontitis mouse model, providing a theoretical foundation for the study of bone repair in periodontitis.
研究领域:
口腔医学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Heng Yongqing,Liang Yupei,Zhang Junqian,Li Lihui,Zhang Wenjuan,Jiang Yanyu,Wang Shiwen,Jia Lijun
The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Huanqi Zhang,Xiaozhe Chen,Fuqing Liu,Yanju Bi,Meichen Gao,Xiaojing Li
Long-term environmental exposure to chlorpyrifos (CPF) can cause intestinal damage. Baicalein (BAI) helps aquatic organisms resist environmental pollution stress. Adenosine 5′-monophosphate activated protein kinase (AMPK) is a key molecule in energy regulation; however, the mechanism by which BAI inhibits CPF-induced autophagy/ferroptosis remains unclear. Based on reported environmental concentrations and IC 50 values of CPF, we established models using the midgut of carp and Epithelioma papulosum cyprini (EPC) cells exposed to CPF with or without BAI treatment. Transcriptomics and network pharmacology were used to analyze the key pathways affected by CPF and BAI. Tissue damage, cell cycle regulation, autophagy, ferroptosis, and mitochondrial function were assessed. The effect of BAI on AMPK–unc-51-like autophagy-activating kinase 1 (ULK1) binding was confirmed by molecular dynamics simulation, co-immunoprecipitation, and laser confocal analysis. In addition, the regulatory impact of an AMPK activator on the autophagy/ferroptosis axis was examined. Results indicated that BAI alleviated CPF-induced pathological changes and mitochondrial damage. CPF exposure caused tight junction disruption, mitochondrial depolarization, and reactive oxygen species and mitochondrial reactive oxygen species production. Transcriptomic analysis revealed that CPF toxicity is related to phagosomes, cell cycle regulation, and ferroptosis. By targeting AMPK, BAI prevents the formation of the AMPK–ULK1 complex and inhibits the CPF-induced cascade involving excessive autophagy, cell cycle arrest, and ferroptosis. In conclusion, BAI targets AMPK to prevent binding with ULK1, thereby suppressing the CPF-activated autophagy/ferroptosis axis, reversing mitochondrial dysfunction, and restoring intestinal homeostasis.
研究领域:
环境毒理学
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分子生物学
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药理学
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细胞生物学
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生态毒理学
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Lu Xiu,Rongguang Ge,Siyu Lu,Linwei Li,Wenqi Huang,Guojun Du,Zengli Zhang,Jie Zhang,Zhongxiao Wan,Jie Chang
Diabetes, a ruthless chronic metabolic disorder, is increasingly considered to jeopardize global well-being over the decades. Royal jelly (RJ) is a complex natural product secreted by worker bees containing a unique fatty acid known as 10-hydroxy-2-decenoic acid (10-HDA). This study aimed to verify the protective effect on cognitive function of RJ and 10-HDA in diabetic mice and explore the underlying mechanism. Briefly, our animal experiment results suggested that 10-HDA had a significant hypoglycemic effect and improved cognitive performance. Through western blotting, RJ and 10-HDA intervention notably increased Atg7, Atg16L1, Beclin-1, Atg5, Atg12, Atg3, and LC3-II expression and decreased p62 expression. Meanwhile, decreased mTOR expression and increased ULK1 expression were also observed in the 10-HDA intervention group. In conclusion, 10-HDA can regulate mTOR/ULK1 pathway to activate autophagy to alleviate hippocampal damage, thereby improving cognitive function in mice with diabetes, which may provide a new option for real-world cognitive impairment management.
研究领域:
医学
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生物学
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DOI
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Xiaoyu Zhu,Fangze Tao,Li Zhang,Yajie Yu,Yanchao Xu,Gang Yang,Zhifeng Wei,Yidong Cheng,Xuelai Yin,Xinyuan Zhang,Wu Wei,Anxi Wang
Aims. Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organs, on detrusor contractility and bladder wall remodeling process. Methods. Partial BOO (pBOO) was created by urethral occlusion in female rats, followed by oral gavage of different dose of AS-IV or vehicle. Cystometric evaluation and contractility test were performed. Bladder wall sections were used in morphology staining, and bladder tissue lysate was used for ELISA assay. Primary smooth muscle cells (SMCs) derived from detrusor were used for mechanism studies. Results. Seven weeks after pBOO, the bladder compensatory enlarged, and the contractility in response to electrical or chemical stimuli was reduced, while AS-IV treatment reversed this effect dose-dependently. AS-IV also showed beneficial effect on reversing the bladder wall remodeling process, as well as reducing ROS level. In mechanism study, AS-IV activated mitophagy and alleviated oxidative stress via an AMPK-dependent pathway. Conclusion. Out data suggested that AS-IV enhanced the contractility of detrusor and protected the bladder from obstruction induced damage, via enhancing the mitophagy and restoring mitochondria function trough an AMPK-dependent way.
研究领域:
药理学
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泌尿科
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
·
2020
·Vol. 75
·期 4
·321
·
IF 2.598
Cao Qian,Du Hongjiao,Fu Xi,Duan Na,Liu Changhe,Li Xiaodong
Artemisinin is an endoperoxide sesquiterpene lactone from Artemisia annua L with multiple beneficial effects, including anti-inflammation, antioxidant, and vascular protection. Recent studies have found that inflammation along with autophagy deficiency in macrophages is the possible reason for foam cell accumulation in the intima, which leads to atherosclerotic plaque formation. The primary aims of this study were to explore the inhibiting effect of artemisinin on atherosclerosis in high-fat diet–fed ApoE −/− mice and investigate the probable mechanism. Artemisinin (50 and 100 mg/kg, intragastric administration) treatment effectively inhibited foamy macrophage transformation and decreased atherosclerotic plaque formation in atherosclerotic mice. Moreover, artemisinin promoted AMP-activated protein kinase (AMPK) activation, inhibited mammalian target of rapamycin (mTOR) and uncoordinated-51-like kinase 1 (ULK1) phosphorylation, and increased LC-3II accumulation and P62 degradation, thereby enhancing macrophage autophagy . Besides, the inhibiting effect of artemisinin on mTOR and ULK1 phosphorylation could be abrogated by AMPK knockdown, suggesting AMPK was the essential target of artemisinin on promoting macrophage autophagy . Our study indicated that artemisinin alleviated atherosclerotic lesions by accelerating macrophage autophagy through the AMPK/mTOR/ULK1 pathway.
研究领域:
药理学
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心血管疾病
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分子生物学
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Zhiying Miao,Zhiruo Miao,Shuang Feng,Shiwen Xu
Chlorpyrifos (CPF) is a typical organophosphate insecticide known to has serious toxicological effects on aquatic animals and causes many environmental contamination problems. To assess the effects of CPF on the epithelioma papulosum cyprini (EPC) cells of the common carps from the point of calcium ion (Ca 2+ ) transport, the CPF-exposed EPC models were primarily established, and both AO/EB staining and Annexin V/PI assay with flow cytometry analysis were subsequently implemented to identify that CPF-induced EPC cell apoptosis, in consistent with the up-regulated expression of BAX, Cyt- c , CASP3 and CASP9, and down-regulated BCL-2 expression. Then, Mag-Fluo-4 AM, Fluo-4 AM and Rhod-2 AM staining probes were co-stained with ER-Tracker Red and Mito-Tracker Green applied to image cellular Ca 2+ flux, illuminating Ca 2+ depleted from ER and flux into mitochondria, resulting in ER stress and mitochondrial dysfunction. Additionally, 2-Aminoethyl Diphenylborinate (2-APB), 4-Phenylbutyric acid (4-PBA) and Dorsomorphin (Compound C) were performed as the inhibitor of Ca 2+ transition, ER stress and AMPK phosphorylation, suggesting CPF-mediated Ca 2+ overload triggered ER stress. And the over-generation of Mito-ROS intensified oxidative stress , promoting the phosphorylation of AMPK and deteriorating cell apoptotic death. The results of this study demonstrated Ca 2+ overload-dependent mitochondrial dysfunction engages in the CPF-induced apoptosis, providing a novel concept for investigating the toxicity of CPF as environmental pollution on aquatic organisms .
研究领域:
毒理学
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环境科学
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细胞生物学
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水生生物学
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DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2022
·Vol. 48
·期 6
·1-11
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IF 4.136
Haoran Miao,Hongliang Hui,Huaming Li,Yangui Lin,Dan Li,Min Luo,Bo Jiang,Yiqian Zhang
Current investigations suggest that pigment epithelial‑derived factor (PEDF) can mediate the progression of non‑small cell lung cancer (NSCLC) by regulating autophagy. However, the underlying mechanisms associated with autophagy remain poorly elucidated. The aim of the present study was to investigate the association between the PEDF/adenosine 5'‑monophosphate‑activated protein kinase (AMPK)/Unc‑51 like autophagy‑activated kinase 1 (ULK1) pathway and autophagy in NSCLC. Intracellular autophagy was evaluated using indicators such as the expression and activation of microtubule‑associated protein light chain 3‑I (LC3‑I), LC3‑II and p62, as well as the distribution and number of autophagosomes observed by confocal microscopy. In addition, the activity and proliferative capacity of NSCLC cells under PEDF overexpression was also examined using Cell Counting Kit‑8 and lactate dehydrogenase (LDH) assays, and western blotting (WB) of related proteins. The results revealed that PEDF significantly inhibited NSCLC cell proliferation and viability, and increased LDH release and intercellular adhesion. Furthermore, PEDF suppressed the expression and activation of LC‑3 and reduced the number and distribution of autophagosomes. The PEDF‑induced inhibition of autophagy exhibited a direct association with the suppressed proliferation capacity and cell viability of NSCLC cells. The results of WB showed that NSCLC cells regulated autophagy through the AMPK/ULK1 signaling pathway. PEDF downregulated the AMPK/ULK1 signaling pathway, and AMPK or ULK1 overexpression markedly reduced the inhibitory effect of PEDF on autophagy. In conclusion, PEDF overexpression significantly inhibited the proliferative capacity and cell viability of NSCLC cells, as PEDF exerted an inhibitory function by regulating autophagy in NSCLC cells. Finally, it was demonstrated that autophagy may be suppressed by inhibiting the AMPK/ULK1 signaling pathway, thereby revealing a mechanism of lung cancer progression.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2022
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IF 5.572
Xinyue Sun,Wenyue Zhang,Yuqi Wang,Yilei Zhang,Xiaojing Liu,Xu Shi,Shiwen Xu
Di(2-ethylhexyl) phthalate (DEHP) and polystyrene microplastics (PS-MPs) are new environmental pollutants that attracted increased attention. At present, the effects and underlying mechanisms of action of combined exposure of DEHP and PS-MPs on the kidney have not been elucidated. To investigate the renal toxicity of DEHP and PS-MPs exposure, we established single and combined DEHP and PS-MPs exposure models in mice and HEK293 cells, respectively. Hematoxylin and eosin staining, transmission electron microscopy , monodansylcadaverine staining, immunofluorescence, real-time quantitative PCR, Western blot analysis and other methods were used to detect relevant indicators. The results showed that the expression levels of ROS/AMPK/ULK1 and Ppargc1α/Mfn2 signaling pathway-related genes were significantly increased in the DEHP and PS-MPs exposure models. The mRNA and protein expression levels of autophagy markers were also upregulated. In addition, we found that the expression levels of mRNAs and proteins in the combined exposure group were more significantly increased than those in the single exposure group. In conclusion, combined exposure to DEHP and PS-MPs caused oxidative stress and activated the AMPK/ULK1 pathway, thereby inducing renal autophagy. Our results enhance the field of nephrotoxicity studies of plasticizers and microplastics and provide new light on combined toxicity studies of DEHP and PS-MPs.
研究领域:
毒理学
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环境科学
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分子生物学
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肾脏生理学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2018
·Vol. 18
·期 6
·5445-5454
·
IF 1.922
Yang Su,Jingxiao Lu,Pian Gong,Xianguo Chen,Chaozhao Liang,Jie Zhang
Acute kidney injury (AKI) is a clinically common and severe complication of ischemia‑reperfusion (I/R), associated with high morbidity and mortality rates, and prolonged hospitalization. Rapamycin is a type of macrolide, primarily used for anti‑rejection therapy following organ transplantation and the treatment of autoimmune diseases. Rapamycin has been identified to exert a protective effect against AKI induced by renal I/R as an autophagy inducer. However, whether rapamycin preconditioning may relieve AKI following cerebral I/R (CIR) remains to be fully elucidated. The purpose of the present study was to investigate the effects of CIR on the renal system of rats and the role of rapamycin in AKI following CIR. In the present study, a CIR model was established in Sprague‑Dawley rats via a 90‑min period of middle cerebral artery occlusion and 24 h reperfusion, and pretreatment with an intraperitoneal injection of rapamycin (dosage: 1 mg/kg; 0.5 h) prior to CIR. The levels of serum creatinine and blood urea nitrogen (BUN), and the expression of inflammation‑, apoptosis‑ and autophagy‑associated markers were subsequently measured. In addition to certain histopathological alterations to the kidney, it was identified that CIR significantly increased the levels of serum creatinine, BUN, tumor necrosis factor‑α and interleukin‑1β, and significantly induced apoptosis and autophagy. It was observed that rapamycin induced autophagy through the mammalian target of rapamycin complex 1/autophagy‑related 13/unc‑51 like autophagy activating kinase 1 signaling pathway, and that rapamycin pre‑treatment significantly improved renal function and alleviated renal tissue inflammation and cell apoptosis in rats following CIR. In conclusion, the results suggested that rapamycin may alleviate AKI following CIR via the induction of autophagy.
研究领域:
药理学
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肾病学
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神经病学
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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
THERIOGENOLOGY
·
2024
·
IF 2.4
Xiu-Li Zhang,Zhi-Yong An,Gao-Jie Lu,Tuo Zhang,Cheng-Wei Liu,Meng-Qi Liu,Qing-Xin Wei,Lin-Hu Quan,Jin-Dan Kang
Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1 . Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.
研究领域:
生殖生物学
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分子生物学
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细胞生物学
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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）