JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
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2025
·Vol. 39
·期 9
·e70453
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IF 2.8
Dongfang Hu,Zihui Shen,Xueke Hou,Zhishuai Wan,Xiaoyu Guo,Lingli Chen,Zhihong Yin,Hongmei Ning,Yaming Ge
Florfenicol (FLO), a widely used antibiotic, can cause early embryonic death and impaired angiogenesis. However, the mechanism by which FLO inhibits angiogenesis and its role in FLO-induced embryonic toxicity are not yet fully understood. This study aimed to investigate the effect of FLO on the proliferation and migration of mouse bEnd.3 endothelial cells (bECs) and the underlying mechanism, given the crucial role of endothelial cells in angiogenesis. The results showed that FLO treatment at 7.5–15 μg/mL significantly inhibited proliferation and migration in a time-dependent manner, with stronger effects observed after 48 h compared to 24 h. RNA sequencing analysis identified 1351 genes differentially expressed in response to FLO. Functional analysis indicated that FLO disrupted ATP metabolism, angiogenesis, vasculature development, and actin filament organization. The F-actin cytoskeleton remodeling was morphologically confirmed, and activation of the ROCK/Cofilin signaling pathway was detected. Subsequent experiments demonstrated that pharmacological inhibition of the pathway normalized cytoskeletal rearrangement and promoted angiogenesis, as evidenced by enhanced wound closure and increased cell viability. Our results demonstrated that ROCK-mediated F-actin remodeling plays a crucial role in the FLO-induced inhibition of proliferation and migration in bECs. These findings may explain why FLO inhibited angiogenesis. However, further investigations are necessary to validate our findings in in vivo experiments.
研究领域:
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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毒理学
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发育生物学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Chenjiao Miao,Zuoyao Wu,Yafei Sun,Zheng Cao
Deoxynivalenol (DON) poses a serious global food safety risk due to its high toxicity and contamination rate. It disrupts the intestinal epithelial barrier, allowing exogenous toxins to enter the circulation and resulting in sepsis and systemic toxicity. In this research, 32 male Kunming mice and Porcine Small Intestinal Epithelial (IPEC-J2) cells were treated with DON at 0–4.8 mg/kg (7 d) and 0–12 μM (24 h), respectively. Histopathological results revealed that DON disrupted the intestinal epithelial barrier, causing apoptosis and tight junction (TJ) injury. Immunofluorescence and protein expression results showed that DON-induced p53-dependent mitochondrial pathway apoptosis and fibrillar actin (F-actin)-associated TJ injury and that the RhoA/ROCK pathway were activated in mice jejunal tissue and IPEC-J2 cells. Pretreatment with RhoA or ROCK inhibitors (Rosin or Y-27632) maintained DON-induced apoptosis and F-actin-associated TJ injury in IPEC-J2 cells. Thus, DON induces damage to the intestinal epithelial barrier through the RhoA/ROCK pathway-mediated apoptosis and F-actin-associated TJ disruption.
CAS / MDL:
研究领域:
毒理学
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细胞生物学
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食品科学
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DOI
PubMed
高影响因子
PLoS Pathogens
·
2021
·Vol. 17
·期 12
·e1010145
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IF 6.823
Kaiyu Chen,Siyuan Zhang,Yina Shao,Ming Guo,Weiwei Zhang,Chenghua Li
Many members of the nucleotide-binding and oligomerization domain (NACHT)- and leucine-rich-repeat-containing protein (NLR) family play crucial roles in pathogen recognition and innate immune response regulation. In our previous work, a unique and Vibrio splendidus -inducible NLRC4 receptor comprising Ig and NACHT domains was identified from the sea cucumber Apostichopus japonicus , and this receptor lacked the CARD and LRR domains that are typical of common cytoplasmic NLRs. To better understand the functional role of AjNLRC4, we confirmed that AjNLRC4 was a bona fide membrane PRR with two transmembrane structures. AjNLRC4 was able to directly bind microbes and polysaccharides via its extracellular Ig domain and agglutinate a variety of microbes in a Ca 2+ -dependent manner. Knockdown of AjNLRC4 by RNA interference and blockade of AjNLRC4 by antibodies in coelomocytes both could significantly inhibit the phagocytic activity and elimination of V . splendidus . Conversely, overexpression of AjNLRC4 enhanced the phagocytic activity of V . splendidus , and this effect could be specifically blocked by treatment with the actin-mediated endocytosis inhibitor cytochalasin D but not other endocytosis inhibitors. Moreover, AjNLRC4-mediated phagocytic activity was dependent on the interaction between the intracellular domain of AjNLRC4 and the β-actin protein and further regulated the Arp2/3 complex to mediate the rearrangement of the cytoskeleton and the polymerization of F-actin. V . splendidus was found to be colocalized with lysosomes in coelomocytes, and the bacterial quantities were increased after injection of chloroquine, a lysosome inhibitor. Collectively, these results suggested that AjNLRC4 served as a novel membrane PRR in mediating coelomocyte phagocytosis and further clearing intracellular Vibrio through the AjNLRC4-β-actin-Arp2/3 complex-lysosome pathway.
Vibrio splendidus is ubiquitously present in marine environments and in or on many aquaculture species and is considered to be an important opportunistic pathogen that has caused serious economic losses to the aquaculture industry worldwide. Phagocytosis is the first step of pathogen clearance and is triggered by specific interactions between host pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) from invasive bacteria. However, the mechanism that underlies receptor-mediated V . splendidus phagocytosis is poorly understood. In this study, an atypical AjNLRC4 receptor without LRR and CARD domains was found to serve as the membrane receptor for V . splendidus , not the common cytoplasmic NLRs. The Ig domain of AjNLRC4 is replaced with a conventional LRR domain to bind V . splendidus , and the intracellular domain of AjNLRC4 specifically interacts with β-actin to mediate V . splendidus endocytosis in an actin-dependent manner. Endocytic V . splendidus is ultimately degraded in phagolysosomes. Our findings will contribute to the development of novel strategies for treating V . splendidus infection by modulating the actin-dependent endocytosis pathway.
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高影响因子
EUROPEAN JOURNAL OF NEUROSCIENCE
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2022
·Vol. 57
·期 1
·64-77
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IF 3.698
Weimin Ni,Jie Zhang,Bing Wang,Feng Liang,Long Bao,Pengfei Li,Yan Fang
Obesity is a major health crisis in the modern society. Studies have shown that the consumption of a high-fat diet (HFD) induces hypothalamic inflammation and leptin resistance, which consequently favours body mass gain. Actin related protein 2/3 complex subunit 1 (ARPC1B), an actin-binding protein, is highly expressed in immune cells. Recent studies have shown that ARPC1B has a certain anti-inflammatory effect. While ARPC1B expression is decreased in the hypothalamus of mice fed a HFD, the role of ARPC1B in HFD-induced obesity remains unclear. Thus, we investigated whether ARPC1B up-regulation in the hypothalamic arcuate nucleus (ARC) could inhibit the development of obesity. Herein, ARPC1B overexpression lentiviral particles were stereotaxically injected into the ARC of male C57BL/6J mice (7 weeks old) fed with HFD. Overexpression of ARPC1B in the hypothalamic ARC attenuated HFD-induced ARC inflammation, reduced body-weight gain and feed efficiency. Furthermore, up-regulation of ARC ARPC1B improved the glucose tolerance and reduced subcutaneous/epididymal fat mass accumulation, which decreased the serum total cholesterol, serum triglyceride and leptin levels. In addition, upon ARPC1B overexpression in the hypothalamic ARC, intraperitoneal injection of leptin increased the phosphorylation level of signal transducer and activator of transcription 3 (STAT3), an important transcription factor for leptin's action, in the ARC of obese mice. Accordingly, we suggest that up-regulation of ARPC1B in the hypothalamic ARC may improve the HFD-induced hypothalamic inflammation and leptin resistance. Our findings demonstrate that ARPC1B is a promising target for the treatment of diet-induced obesity.
研究领域:
神经科学
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代谢学
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内分泌学
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免疫学
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分子生物学
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PubMed
高影响因子
Oncology Letters
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2022
·Vol. 24
·期 5
·1-12
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IF 3.111
Haoran Jiang,Xianxin Wen,Xue Zhang,Bingyu Zhang
Concanavalin A (Con A), the first and most typical representative of the legume lectin family, has a potent anti‑liver cancer effect by inducing cell apoptosis and autophagy. However, its function in human liver cancer cell migration remains unclear. The present study investigated the effect of Con A on the viability and migration of human liver cancer cells with different metastatic abilities. It was found that Con A could reduce the viability of human liver cancer cells (HCCLM3, MHCC97L and HepG2) and human hepatocytes (MIHA). In addition, Con A could inhibit human liver cancer cell migration specifically without affecting hepatocytes. Sugar inhibition assay showed that glucose‑related sugar binding sites played an important role in the inhibition of Con A on human liver cancer cell migration. In addition, Con A could affect HCCLM3 migration by activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway. Moreover, Con A could regulate fibrous actin (F‑actin) redistribution and assembly via the MAPK signaling pathway. However, Con A had no significant effect on the activation of matrix metalloproteinase (MMP)‑2 and MMP‑9 in HCCLM3 cells. In conclusion, Con A may bind to glucose‑related receptor protein, activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway, further contracting cells and reducing the content of F‑actin of single cells to inhibit HCCLM3 cell migration. These results would deepen the links between human liver cancer cell migration and related glycoproteins or signaling molecules, and may provide a new perspective for Con A as a potential anticancer agent.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
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药理学
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PubMed
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2023
·
IF 1.6
Xuena Zhang,Jie Li
ObjectivesTo observe changes in actin and dendritic spines in the hippocampus after propofol anesthesia, and to evaluate the role of these changes in subsequent learning impairment in both young (3-month-old) and aged (20-month-old) male rats.MethodsThe shuttle box test was used to evaluate learning from 1, 3, 7, or 14 days after anesthesia. Both F-actin content and dendritic spines in the hippocampal CA1 region were observed using immunofluorescent staining and western blot assays.ResultsThe latency of the escape response was significantly prolonged until 7 days after anesthesia in the aged rats, and their learning curves were shifted. Dendritic spines were also decreased in the aged rats within 7 days after anesthesia, and F-actin content was significantly increased until 14 days after anesthesia.ConclusionsLearning was inhibited after propofol anesthesia, especially in aged rats. The over-polymerization of actin and subsequent reorganization of dendritic spines in the hippocampus may be responsible for this learning impairment. Our findings suggest that synaptic plasticity may be an underlying mechanism of perioperative neurocognitive disorders.
研究领域:
神经科学
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药理学
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认知科学
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高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2023
·
IF 4.9
Yuying Bai,Dawei Tian,Zhengxin Ren,Dangyang Yue,Qian Ren,Li Pei,Jun Pan
Though magnetic iron oxide nanoparticles (IONPs) are approved for clinical use as contrast agents for MR imaging in United States and Europe, and are widely used to label cells in research, the relationship between IONPs and mesenchymal stem cells (MSCs) is not fully addressed. Here the effects of consistently appeared γ-Fe 2 O 3 on the lineage commitment of MSCs were studied to optimize applications of IONPs in MSCs upon verification of viability. 30 nm 10 μg/mL induced highest promotions on osteogenesis, while 30 and 50 nm of 100 μg/mL elicited most chondrogensis in 14 days, where the effects on ALP, GAG and SOX9 appeared after 7 days, while on RUNX2 came out after 10 days. γ-Fe 2 O 3 enhanced intracellular and extracellular Fe 3+ and ROS, modulated F-actin and decreased Lamin A of MSCs at different time scale. The disturbances of F-actin, Lamin A or ROS altered the effects of γ-Fe 2 O 3 on MSC differentiation. Our results demonstrate that different size, concentration and modulation of γ-Fe 2 O 3 are needed in its MSC applications for bone and cartilage tissues. Furthermore, an undocumented phenomenon that the modulation of F-actin affected the Lamin A expression in MSCs was observed.
研究领域:
纳米技术
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干细胞生物学
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生物医学工程
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材料科学
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细胞生物学
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PubMed
高影响因子
Journal of Oncology
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2022
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IF 4.501
Weiwei Wang,Lipei Wu,Jiale Tian,Wenhui Yan,Chunrun Qi,Wuchao Liu,Shihai Xuan,Anquan Shang
Application of extracellular vesicles (EVs) for cancer treatment has been well-documented. We probed into the potential role of cervical cancer cells-secreted EVs by transferring miR-146a-5p in cervical cancer. After characterization of miR-146a-5p expression in clinical cervical cancer tissue samples, gain- and loss-of-function experiments were implemented to test the effect of miR-146a-5p on the invasion, epithelial-mesenchymal transition (EMT), and anoikis in cervical cancer cells. EVs were isolated from high-metastatic cervical cancer cells, after which their effects on the malignant behaviors of low-metastatic cervical cancer cells were assessed in a co-culture system. Luciferase assay was implemented to validate the putative binding relationship between miR-146a-5p and WWC2, followed by further investigation of downstream pathway (Hippo-YAP). Finally, nude mouse lung metastasis model was developed for in vivo validation. miR-146a-5p was elevated in cervical cancer tissues and high miR-146a-5p expression promoted the metastatic potential of cervical cancer cells through enhancing their invasiveness and anoikis resistance, and inducing EMT. Furthermore, miR-146a-5p carried by EVs secreted by highly metastatic cervical cancer cells could promote the metastasis of low-metastatic cervical cancer cells. Mechanistically, miR-146a-5p targeted WWC2 to activate YAP, by which it inhibited the phosphorylation of cofilin, and promoted the process of cofilin-mediated depolymerization of F-actin to G-actin. In vivo data demonstrated that EVs-carried miR-146a-5p promoted tumor metastasis through the WWC2/YAP axis. Cancer-derived EVs delivered pro-metastatic miR-146a-5p to regulate the actin dynamics in cervical cancer, thereby leading to cancer metastasis. This experiment highlighted an appealing therapeutic modality for cervical cancer.
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
Cell Reports
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2023
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IF 8.8
Yingqi Liu,Xuemei Yao,Youbo Zhao,De Fang,Lei Shi,Li Yang,Guanbin Song,Kaiyong Cai,Liqi Li,Qin Deng,Menghuan Li,Zhong Luo
The tumor microenvironment (TME) plays decisive roles in disabling T cell-mediated antitumor immunity, but the immunoregulatory functions of its biophysical properties remain elusive. Extracellular matrix (ECM) stiffening is a hallmark of solid tumors. Here, we report that the stiffened ECM contributes to the immunosuppression in TME via activating the Rho-associated coiled-coil-containing protein kinase (ROCK)-myosin IIA-filamentous actin (F-actin) mechanosignaling pathway in tumor cells to promote the generation of TRIM14-scavenging nonmuscle myosin heavy chain IIA (NMHC-IIA)-F-actin stress fibers, thus accelerating the autophagic degradation of cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) to deprive tumor cyclic GMP-AMP (cGAMP) and further attenuating tumor immunogenicity. Pharmacological inhibition of myosin IIA effector molecules with blebbistatin (BLEB) or the RhoA upstream regulator of this pathway with simvastatin (SIM) restored tumor-intrinsic cGAS-mediated cGAMP production and enhanced antitumor immunity. Our work identifies that ECM stiffness is an important biophysical cue to regulate tumor immunogenicity via the ROCK-myosin IIA-F-actin axis and that inhibiting this mechanosignaling pathway could boost immunotherapeutic efficacy for effective solid tumor treatment.
研究领域:
癌症生物学
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免疫学
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细胞生物学
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生物物理学
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DOI
PubMed
高影响因子
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