Food & Nutrition Research
·
2022
·
IF 3.221
Tian Su,Zhen Wang,Zhengyi Zhang,Zhanwu Hou,Xiao Han,Fei Yang,Huadong Liu
Background Resveratrol, a well-known natural compound and nutrient, activates the deacetylation ability of SIRT1, demonstrating p53-dependent apoptosis functions in many diseases. However, the nascent proteomic fluctuation caused by resveratrol is still unclear. Objective In this study, we investigated the effect of resveratrol on the nascent proteome and transcriptome initiated by SIRT1 activation, and we explored the mechanism of resveratrol in HEK 293T cells. Methods Bioorthogonal noncanonical amino acid tagging (BONCAT) is a method used to metabolically label nascent proteins. In this strategy, L-azidohomoalanine (AHA) was used to replace methionine (Met) under different conditions. Taking advantage of the click reaction between AHA and terminal alkyne- and disulfide-functionalized agarose resin (TAD resin), we were able to efficiently separate stimulation responsive proteins from the pre-existing proteome. Resveratrol responsive proteins were identified by Liquid Chromatograph-Mass Spectrometer/Mass Spectrometer (LC-MS/MS). Furthermore, changes in mRNA levels were analyzed by transcriptome sequencing. Results Integrational analysis revealed a resveratrol response in HEK 293T cells and showed that Hsp60 was downregulated at both the nascent protein and mRNA levels. Knockdown of SIRT1 and Hsp60 provides evidence that resveratrol downregulated Hsp60 through SIRT1 and that Hsp60 decreased p53 through the Akt pathway. Conclusions This study revealed dynamic changes in the nascent proteome and transcriptome in response to resveratrol in HEK 293T cells and demonstrated that resveratrol downregulates Hsp60 by activating SIRT1, which may be a possible mechanism by which resveratrol prevents p53-dependent apoptosis by regulating Hsp60.
研究领域:
分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2026
·
IF 4.7
Zhichao Yu,Lan Hu,Jing Ding,Xiang Li,Qi Zhang,Qiaoyu Zhang,Shuoyu Chen,Pei Zhang,Jiaqi Zhang,Baoping Jiang,Xueping Zhou,Lingling Zhou
Background The mitochondrial unfolded protein response (UPR mt ) maintains proteostasis, but its dysregulation dictates cell fate. This study aimed to elucidate the signaling mechanism by which triptolide (TP), a bioactive component of Tripterygium wilfordii Hook. f., triggers hepatocellular Lipoapoptosis, focusing on HSP60-mediated UPR mt overactivation. Methods A TP-induced mouse liver injury model was established. Serum biochemistry, histopathology, and liver proteomics were performed. Key proteins (HSP60, UPR mt components, SREBP-1c, FASN, cleaved caspase-3) were validated by Western blot and RT-qPCR both in vivo and in AML-12 hepatocytes, while co-immunoprecipitation (Co-IP) was conducted in AML-12 cells. Functional validation used siRNA knockdown. Results TP induced liver injury, lipid deposition, and apoptosis. Proteomic screening implicated UPR mt activation, with HSP60 subsequently validated as a central upregulated component. TP downregulated MFN2 and upregulated HSP60, ClpP, DRP1, SREBP-1c, FASN, and cleaved caspase-3. Co-IP confirmed a direct HSP60–SREBP-1c interaction. Moreover, HSP60 knockdown attenuated the entire TP-induced cascade, including UPR mt overactivation, mitochondrial dysfunction, lipid dysregulation, and apoptosis. Conclusion This study delineates a novel mitochondria-to-nucleus pathway wherein TP induces HSP60-mediated UPR mt overactivation, which promotes SREBP-1c/FASN-driven lipid accumulation, culminating in lipoapoptosis. The “HSP60–UPR mt –SREBP-1c/FASN–lipoapoptosis” axis links dysregulated organelle stress signaling to metabolic cell death. These findings establish HSP60 as a key signaling node and a potential therapeutic target for intercepting this pathological cascade.
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
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IF 7.6
Xin-Ran Ge,Yi Zhao,Hao-Ran Ren,Fu-Wei Jiang,Shuo Liu,Ming Lou,Yi-Feng Huang,Ming-Shan Chen,Jia-Xin Wang,Jin-Long Li
As the most produced phthalate, di-(2-ethylhexyl) phthalate (DEHP) is a widely environmental pollutant primarily used as a plasticizer, which cause the harmful effects on human health. However, the impact of DEHP on spleen and its underlying mechanisms are still unclear. Pyroptosis is a novel form of cell death induced by activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and implicated in pathogenesis of numerous inflammatory diseases. The current study aimed to explore the impact of DEHP on immune inflammatory response in mouse spleen. In this study, the male ICR mice were treated with DEHP (200 mg/kg) for 28 days. Here, DEHP exposure caused abnormal pathohistological and ultrastructural changes, accompanied by inflammatory cells infiltration in mouse spleen. DEHP exposure arouse heat shock response that involves increase of heat shock proteins 60 (HSP60) expression. DEHP also elevated the expressions of toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) proteins, as well as the activation of NF-κB pathway. Moreover, DEHP promoted NLRP3 inflammasome activation and triggered NLRP3 inflammasome-induced pyroptosis. Mechanistically, DEHP drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis. Our findings reveal that targeting HSP60-mediated TLR4/NLRP3 signaling axis may be a promising strategy for inflammatory diseases treatment.
研究领域:
毒理学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2026
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IF 4.7
Ren Mei,Zhou Haiqian,Dong Hu,Wu Jinen,Wang Jianing,Yu Jiaxi,Guo Huichen,Sun Shiqi
Foot-and-mouth disease virus (FMDV) exhibits greater temperature sensitivity compared to many other picornaviruses, which poses a substantial challenge for the stability of inactivated vaccines. Therefore, enhancing the thermal stability of the FMDV capsid is crucial. FMDV exists as a quasispecies with high mutation rates, providing a basis for selection under pressure. Our group previously discovered that heat shock protein HSP60 was recruited to support FMDV replication by promoting the assembly of the viral replication complex (RC). By applying the HSP60 inhibitor mizoribine, we selected FMDV variants with enhanced fitness under conditions of impaired HSP60 function. Subsequent sequencing of the selected populations and reverse genetics approaches identified a key amino acid substitution, T171P in the viral VP1 protein that confers resistance to the HSP60 inhibitor. Structural simulation predicted that the T171P substitution enhances the stability of the VP1 protein, which was further supported by experimental evidence demonstrating increased thermal stability of the whole viral capsid. A series of experiments, including virion stability assessment using the PaSTRy assay, quantification of intact particles following heat challenge, and evaluation of viral infectivity at elevated temperatures, demonstrated that the T171P-VP1 variant possesses enhanced thermostability compared to the wild-type (WT) virus. Furthermore, immunization experiments showed that the inactivated T171P-VP1 variant, after heat challenge, elicited a stronger neutralizing antibody response than the similarly treated WT virus. This study identifies a novel amino acid substitution that significantly enhances FMDV thermostability. This finding not only provides a viable strategy for improving the thermal stability of FMD vaccines but also opens new avenues for exploring the intricate mechanisms of host-virus interaction. Key points • A novel HSP60 inhibitor-based selection strategy identified the T171P-VP1 substitution conferring enhanced viral fitness. • The T171P substitution significantly improves FMDV capsid thermostability compared to the wild-type virus. • The inactivated T171P-VP1 variant induces stronger neutralizing antibody responses after heat challenge, offering a promising approach for thermostable FMD vaccine development.
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DOI
高影响因子
INFLAMMATION
·
2026
·Vol. 49
·期 1
·41
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IF 5
Zheng-qing Hu,Ruijie Ma,Hang Zhang,Jiahao Miao,Jia-qing Sun,Jinlong Yuan,Jiaqiang Liu,Zihuan Zhang,Dayong Xia
This study aims to elucidate the mechanism by which Heat Shock Protein 60 (HSP60) mediates microglial pyroptosis in the context of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and to investigate the effects of HSP60 inhibition on EBI after SAH. A mouse subarachnoid hemorrhage (SAH) model was established using prechiasmatic cistern blood injection. In vitro, microglia were stimulated with 25 µmol/L oxyhemoglobin (OxyHB) to simulate the SAH pathological environment. In vivo, mice received 100 mg/kg Mizoribine, while in vitro, 80 µmol/L Mizoribine was used to suppress SAH-induced HSP60 upregulation. Techniques including Western blotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, ELISA, modified Garcia neurological scoring, beam walking, brain water content measurement, Morris water maze, TUNEL staining, and Nissl staining were employed to systematically investigate the role of HSP60 inhibition in neuroinflammation and microglial pyroptosis after SAH. Compared to the sham group, both in vivo and in vitro studies with blinded, random sampling of six groups demonstrated a significant increase in HSP60 expression post-SAH. In vivo, 100 mg/kg Mizoribine alleviated blood-brain barrier disruption, cerebral edema, neuronal apoptosis/necrosis, and improved neurological deficits and cognitive impairment. In vitro, 80 µmol/L Mizoribine markedly attenuated microglial activation and pyroptosis, downregulated pro-inflammatory cytokines, and mitigated neuroinflammation. The upregulation of HSP60 after SAH promotes NLRP3 inflammasome assembly by activating the TLR4/MyD88/NF-κB signaling pathway, thereby inducing microglial pyroptosis and exacerbating the progression of early brain injury. Inhibition of HSP60 represents a potential therapeutic strategy for ameliorating EBI after SAH.
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2022
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IF 9.417
Qinglong Guo,Mengyuan Yin,Junjuan Fan,Yafei Yang,Tao Liu,Haisheng Qian,Xingliang Dai,Xianwen Wang
Glioblastoma multiforme (GBM) is the most prevalent malignant brain tumor. It expresses high levels of heat shock protein (HSP60), which is associated with poor prognosis. Chemodynamic therapy (CDT) can be improved by photothermal therapy (PTT) and facilitate tumor eradication. Therefore, it is necessary to develop novel agents that synergize with the tumor killing effects of PTT/CDT by downregulating HSP60. Based on The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases and clinical cases, this study determined that HSP60 was upregulated and associated with reduced overall survival (OS) in GBM patients. Herein, TA-VO x nanobranches (TA-VO x NBs) were successfully synthesized by a one-step self-assembly procedure, which had excellent photothermal conversion characteristics and improved peroxidase-mimicking activity at elevated temperatures. Moreover, TA-VO x NBs can degrade to VO 2+ in a slightly acidic tumor microenvironment. In vitro and in vivo studies showed that TA-VO x NBs synergized with PTT/CDT and improved glioma eradication under 808 nm irradiation due to the heat-induced ROS generation and the inhibition of HSP60. Furthermore, TA-VO x NBs were rapidly cleared by the kidney and showed good biosafety. Combined with the ease of fabrication, this is a promising nanomaterial that can be introduced for clinical translation in cancer therapy.
研究领域:
肿瘤学
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生物医学工程
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纳米医学
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
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IF 8.355
Haixia Liu,Qingzhu Yang,Wei Guo,Huiming Lin,Feng Zhang,Jingxiang Zhao,Tianyue Ma,Le Zhao,Na Xu,Ruiwen Wang,Jingyao Yu,Fengyu Qu
Although phototherapy has received widespread attention in recent years due to its high efficiency, low invasiveness, and minor side effects, there are still few studies on the relationship between phototherapy and immunotherapy. Therefore, non-stoichiometric CoWO 4-x nanoparticles (NPs) were strategically designed and prepared, as these can simultaneously generate hyperthermia and reactive oxygen species (ROS) under near-infrared laser irradiation, illustrating that they can be used to realize photothermal therapy (PTT) and photodynamic therapy (PDT) on tumors. CoWO 4-x NPs not only have strong near-infrared absorption, outstanding biocompatibility, and excellent photothermal stability but they also can be used as photoacoustic (PA) and Computer Tomography (CT) contrast agents for working with tumors. In particular, the relationships between phototherapy, immunogenic cell death (ICD) and immunoresistance are here discussed in depth, and enhanced phototherapy was achieved for the first time by injecting etoposide and ML385, which are two typical inhibitors for HSP60 and NRF2, respectively. Furthermore, the biocompatibility of materials in vivo was demonstrated through a variety of cell experiments, changes in mouse body weight, and histological analyses. Our work highlights the great potentials of non-stoichiometric CoWO 4-x NPs as a kind of multifunctional therapeutic agent for implementing enhanced phototherapy in breast cancer by reducing the immunoresistance of HSP60 and NRF2 toward PTT and PDT.
研究领域:
纳米技术
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癌症治疗
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免疫学
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生物医学工程
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产品关联
DOI
高影响因子
POULTRY SCIENCE
·
2021
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IF 3.352
Chen Yang,Pei Luo,Shi-jian Chen,Zhi-chao Deng,Xin-liang Fu,Dan-ning Xu,Yun-bo Tian,Yun-mao Huang,Wen-jun Liu
ABSTRACT Resveratrol, a natural antioxidant, anti-inflammatory plant extract, was found to have a protective effect in poultry subjected to heat stress. In this study, we strove to characterize resveratrol on intestinal of duck exposed to acute heat stress and investigate the underlying mechanism. A total of 120 Shan-ma ducks (60 days old) were randomly divided into 2 groups. The control group was fed a basal diet, and the resveratrol group was fed a basal diet supplemented with 400 mg/kg resveratrol. Animals in 2 groups were kept at a temperature of 24°C ± 2°C for 15 d. Then, animals of both groups were placed in an artificial climate room at 39°C. Twelve ducks of each group were sacrificed for sampling at 0, 30, and 60 min, respectively. Results indicated that resveratrol increased the ratio of villus height to crypt depth, increased the number of goblet cells, and reduced the histopathological damage of jejunum caused by acute heat stress. Furthermore, the gene expression of heat shock proteins ( HSP60, HSP70 , and HSP90 ) and tight junction proteins ( CLDN1 and OCLN ) was significantly increased in the resveratrol group compared to that in the control groups. Simultaneously, resveratrol significantly activated the SIRT1-NRF1/NRF2 signaling pathways, improved ATP level of jejunum, and increased SOD and CAT antioxidant enzymes activities. In addition, we found that the NF-κB / NLRP3 inflammasome signaling pathways were repressed under acute heat stress. Meanwhile, supplement resveratrol further inhibited the NLRP3 inflammasome pathway, decreased protein level of NLRP3 and caspase1 p20, reduced the secretion of IL-1β. Taken together, our results indicate that resveratrol against the oxidative damage and inflammation injury in duck jejunum induced by heat stress via active SIRT1 signaling pathways.
研究领域:
动物科学
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营养学
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生理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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