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胞外ATP
Scientific Reports · 2017 · IF 4.259

Possible Involvement of F1F0-ATP synthase and Intracellular ATP in Keratinocyte Differentiation in normal skin and skin lesions

Xie Xiaoyun,Han Chaofei,Zeng Weiqi,Chen Chen,Lu Lixia,Liu Queping,Peng Cong,Zhao Shuang,Su Juan,Chen Xiang

The F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase β subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis.

CAS / MDL: 1404-19-9 10083-24-6
研究领域: 细胞生物学 · 分子生物学 · 皮肤病学
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ADVANCED FUNCTIONAL MATERIALS · 2019 ·Vol. 29 ·期 39 ·1904144 · IF 15.621

Size Switchable Nanoclusters Fueled by Extracellular ATP for Promoting Deep Penetration and MRI-Guided Tumor Photothermal Therapy

Zhanwei Zhou,Yadong Liu,Minghua Zhang,Chenzi Li,Ruoxi Yang,Jing Li,Chenggen Qian,Minjie Sun

Protein-based theranostic agents (PBTAs) exhibit superior performance in the diagnosis and therapy of cancers. However, the in vivo applications of PBTA are largely limited by undesired accumulation, penetration, or selectivity. Here, an ATP-supersensitive protein cluster is fabricated for promoting PBTA delivery and enhancing magnetic resonance imaging (MRI)-guided tumor photothermal therapy. Gd 3+ - and CuS-coloaded small bovine serum albumin nanoparticles (GdCuB) are synthesized as the model protein with a size of 9 nm and are encapsulated into charge switchable polycations (DEP) to form DEP/GdCuB nanoclusters of 120 nm. In blood circulation, DEP/GdCuB significantly extends the half-lifetime and thereby enhances the tumor accumulation of GdCuB. When the clusters reach the tumor site, the extracellular adenosine triphosphate (ATP) can effectively trigger the release of GdCuB, resulting in tumoral deep penetration as well as the activation of T 1 -weighted MRI ( r 1 value switched from 2.8 × 10 −3 to 11.8 × 10 −3 m −1 s −1 ). Furthermore, this delivery strategy also improves the tumoral photothermal therapy efficacy with the MRI-guided therapy. The study of ATP-activated nanoclusters develops a novel strategy for tumor deep penetration and on/off imaging of PBTA by size switchable technology, and reveals the potential for MRI-guided therapy of cancers.

研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 磁共振成像 · 药物递送系统
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JOURNAL OF IMMUNOLOGY · 2024 · IF 3.6

ATP-elicited Cation Fluxes Promote Volume-regulated Anion Channel LRRC8/VRAC Transport cGAMP for Antitumor Immunity

Wang Li,Cao Limin,Li Zhihong,Shao Zhugui,Chen Xia,Huang Zhicheng,He Xiaoxiao,Zheng Junke,Liu Li,Jia Xin-Ming,Xiao Hui

The cyclic GMP-AMP synthase (cGAS)–stimulator of IFN genes (STING) pathway is instrumental to antitumor immunity, yet the underlying molecular and cellular mechanisms are complex and still unfolding. A new paradigm suggests that cancer cells’ cGAS-synthesized cGAMP can be transferred to tumor-infiltrating immune cells, eliciting STING-dependent IFN-β response for antitumor immunity. Nevertheless, how the tumor microenvironment may shape this process remains unclear. In this study, we found that extracellular ATP, an immune regulatory molecule widely present in the tumor microenvironment, can potentiate cGAMP transfer, thereby boosting the STING signaling and IFN-β response in murine macrophages and fibroblasts. Notably, genetic ablation or chemical inhibition of murine volume-regulation anion channel LRRC8/volume-regulated anion channel (VRAC), a recently identified cGAMP transporter, abolished ATP-potentiated cGAMP transfer and STING-dependent IFN-β response, revealing a crucial role of LRRC8/VRAC in the cross-talk of extracellular ATP and cGAMP. Mechanistically, ATP activation of the P2X family receptors triggered Ca2+ influx and K+ efflux, promoting reactive oxygen species production. Moreover, ATP-evoked K+ efflux alleviated the phosphorylation of VRAC’s obligate subunit LRRC8A/SWELL1 on S174. Mutagenesis studies indicated that the phosphorylation of S174 on LRRC8A could act as a checkpoint for VRAC in the steady state and a rheostat of ATP responsiveness. In an MC38-transplanted tumor model, systemically blocking CD39 and ENPP1, hydroxylases of extracellular ATP and cGAMP, respectively, elevated antitumor NK, NKT, and CD8+ T cell responses and restrained tumor growth in mice. Altogether, this study establishes a crucial role of ATP in facilitating LRRC8/VRAC transport cGAMP in the tumor microenvironment and provides new insight into harnessing cGAMP transfer for antitumor immunity.

CAS / MDL: 711019-86-2
研究领域: 免疫学 · 癌症生物学 · 细胞生物学 · 分子生物学
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FOOD RESEARCH INTERNATIONAL · 2021 · IF 6.475

Effects of acid, alkaline, cold, and heat environmental stresses on the antibiotic resistance of the Salmonella enterica serovar Typhimurium

Shang Wu,Yang Yang,Tingwei Wang,Jiadi Sun,Yinzhi Zhang,Jian Ji,Xiulan Sun

Antibiotic resistance in Salmonella enterica serovar Typhimurium ( S . ser. Typhimurium) has become a critical safety hazard in food. Sublethal environmental stresses can influence resistance in Salmonella during food processing. This study simulated environmental stresses in food processing. The antibiotic resistance of three strains of S . ser. Typhimurium (the ATCC 14028 strain and two wild-type isolates from chicken and pork product processing) was evaluated under different pH levels (5.0, 5.5, 6.0, 8.0, and 9.0). Also, dynamic changes in resistance with treatment duration under cold (4 °C, −20 °C) and heat (55 °C) treatment were studied. The results showed that acid and alkaline stresses reduced the resistance of S. ser. Typhimurium to eight antibiotics; meanwhile, the resistance of meropenem (MERO) increased. The minimal inhibitory concentration (MIC) of MERO was increased 16- to 64-fold. With acid or alkaline stress, the extracellular ATP content increased, and the scanning electron microscopy (SEM) result clearly revealed the appearance of wrinkles and holes on the outer membrane of Salmonella . These observations imply changes in membrane permeability, which may decrease the antibiotic resistance of Salmonella . Cold or heat stress increased the resistance of S . ser. Typhimurium to tetracycline, cefotaxime, ceftazidime, nalidixic acid, azithromycin, and ampicillin; the MIC increased 2- to 4-fold. The antibiotic resistance only changed when cold and heat stresses occurred over a certain period of time and remained unchanged when the stress persisted. This study reports on the ability of S. ser. Typhimurium to develop antibiotic resistance after environmental stresses. It can provide valuable information for meat processing to improve interventions and risk management.

CAS / MDL: 389-08-2
研究领域: 微生物学 · 食品科学 · 抗菌素耐药性 · 环境压力
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POSTHARVEST BIOLOGY AND TECHNOLOGY · 2021 · IF 5.537

α-Lipoic acid treatment alleviates postharvest pericarp browning of litchi fruit by regulating antioxidant ability and energy metabolism

Mingyang He,Yanfei Wu,Min Hong,Ze Yun,Taotao Li,Yueming Jiang

Litchi fruit has high commercial value and significant benefits for humans. However, pericarp browning, as the indicator of litchi fruit senescence, limits the shelf life of litchi fruit. Effect of α-lipoic acid (α-LA) that has great antioxidant potential, on litchi fruit senescence was investigated. Results showed that α-LA delayed pericarp browning and attenuated redox stress of litchi fruit, indicated by lower hydrogen peroxide (H 2 O 2 ) and superoxide radical (O 2 −· ) contents but higher hydroxy radical scavenging rate. Compared to control, α-LA treatment enhanced enzymatic: superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) as well as nonenzymatic antioxidants: glutathione (GSH) and ascorbate (AsA). Meanwhile, α-LA was protective against oxidative stress by inducing glutaredoxin ( LcGrx ), thioredoxin ( LcTrx ) and methionine sulfoxide reductase ( LcMsr ) expression levels. These α-LA-induced antioxidant systems directly increased the antioxidant capacity. Further research indicated that α-LA pretreatment maintained higher intracellular ATP level and activated extracellular ATP signaling through up-regulating LcDORN1s expression, indirectly increasing the antioxidant capacity. In conclusion, α-LA is effective to increase the antioxidant capacity and delay the pericarp browning of litchi fruit.

CAS / MDL: 1077-28-7
研究领域: 植物科学 · 食品科学 · 生物化学 · 分子生物学
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