JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Wei Yang,Yu Li,Ruzhen Feng,Peiyao Liang,Kefan Tian,Lingli Hu,Kejing Wang,Tianming Qiu,Jingyuan Zhang,Xiance Sun,Xiaofeng Yao
Perfluorooctane sulfonate (PFOS), a listed persistent organic pollutant, poses risks to human health and is closely linked to chronic metabolic diseases. Although the role of mitochondrial fission in these diseases has garnered attention, whether and how PFOS induces mitochondrial fission remains obscure. Here, we found that PFOS induced mitochondrial fission, as demonstrated by the fragmentation of mitochondria and the upregulation of dynamin-related protein 1 (DRP1), phospho-DRP1 and mitochondrial fission protein 1 (FIS1) in human hepatocytes MIHA and mice liver. Blocking the calcium transfer from lysosomes to mitochondria that was executed by transient receptor potential mucolipin 1 (TRPML1) of lysosomes and voltage-dependent anion channel 1 (VDAC1) of mitochondria, did not affect PFOS-induced mitochondrial fission. In contrast, knockdown of TRPML1 or VDAC1 reversed this process. Knockdown of mitochondrial calcium uniporter (MCU), rather than inhibiting its activity, effectively alleviated PFOS-induced mitochondrial fission. Additionally, PFOS increased MCU oligomers without affecting MCU monomer. Inhibiting autophagy reversed the MCU oligomerization. Further investigation unveiled the interactions of MCU with VDAC1, TRPML1, mitochondrial Fo complex subunit F2 (ATP5J2) and DRP1 in PFOS-exposed mice liver and MIHA cells. We also discovered that knockdown of ATP5J2 alleviated PFOS-induced mitochondrial fission. Ulteriorly, PFOS upregulated ATP5J2 that underwent oligomerization. Knockdown of MCU reversed the increase in ATP5J2. Our study uncovers the presence and molecular basics of lysosomes-regulated mitochondrial fission under PFOS exposure, explains the regulatory pathways on MCU and ATP5J2 oligomerization and their pivotal roles in mitochondrial fission, highlighting the involvement of mitochondrial fission in PFOS-related health risks.
研究领域:
细胞生物学
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毒理学
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代谢疾病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2019
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IF 6.361
Jinhui Huang,Jianglin Hu,Yahui Shi,Guangming Zeng,Wenjian Cheng,Hanbo Yu,Yanling Gu,Lixiu Shi,Kaixin Yi
Recently, the application of membranes faces a big challenge due to membrane fouling, to alleviate this situation, the hybridization of photocatalysis and membrane filtration has aroused significant attention. In this study, we firstly introduced melamine, cyanuric acid and urea in dimethyl sulfoxide (DMSO) as precursors to fabricated the MCU(DMSO)-C 3 N 4 material with excellent photocatalytic performance, and immobilized it on PVDF membranes by vacuum filtration, subsequently adding polyethylene glycol and glutaraldehyde as crosslinkers from MCU-C 3 N 4 /PVDF membrane. The results demonstrate that with the MCU-C 3 N 4 ratio increasing, the membrane flux was gradually decreased. Besides, the photocatalytic efficiencies of MCU-C 3 N 4 /PVDF for rhodamine B (RhB) and tetracycline hydrochloride (TC) degradation are 84.24% and 71.26% respectively, which are about 8 times higher than that of the original membrane. To evaluate antifouling performance of photocatalytic membranes, we conducted a four-stage filtration system, and the flux recovery ratio (FRR) of MCU-C 3 N 4 /PVDF membranes reached over 80% (optimum 91%) under visible light irradiating (λ > 420 nm) for 30 min. Meanwhile, under visible light irradiation reversible fouling (Rr) gradually became the dominant fouling factor instead of the irreversible fouling (Rir), indicating the excellent antifouling performance of MCU-C 3 N 4 /PVDF membranes. This novel method to modify membranes with MCU-C 3 N 4 gives insight to photocatalytic and self-cleaning properties of photocatalytic composite membranes, providing theoretical basis for their broad application.
研究领域:
环境科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2026
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IF 12.2
Shixian Pi,Wanling Liu,Junyong Zhao,Hui Chen,Xianbin Luo,Shaofa Wu,Jiarou Song,Xun Chen,Xue Li,Wenjian Luo,Yirui Wang,Chuan Liu,Jun Ren,Tian Li,He Liu,Xiaoyong Tong,Zhexue Qin
Vascular calcification arises from osteogenic transdifferentiation of vascular smooth muscle cells (VSMC) driven by disordered calcium signaling. Sarcoplasmic/ER calcium ATPase 2 (SERCA2) maintains intracellular calcium homeostasis. Irreversible oxidation of SERCA2 Cys 674 (C674) indicates SERCA2 dysfunction. The impact of SERCA2 dysfunction on vascular calcification remains poorly understood. Here, we demonstrate that oxidized SERCA2 C674, a SERCA2 dysfunction marker, was elevated in the calcified arteries of mice and chronic kidney disease (CKD) patients. Heterozygous SERCA2 Cys674Ser knock-in (SKI) mice, a SERCA2 dysfunction model, exhibited aggravated aortic calcification in cholecalciferol (VitD3)-overloaded and 5/6 nephrectomy-induced CKD mice. SERCA2 dysfunction exacerbates calcification, mitochondrial impairment and calcium overload in cultured VSMC. Mechanistically, SERCA2 dysfunction increased mitochondria-associated endoplasmic reticulum membrane (MAM) formation. Furthermore, outer-mitochondrial translocator protein (TSPO) was identified to facilitate SERCA2 coupling to the IP3R1-Grp75-VDAC1-MCU complex at MAM. TSPO knockdown alleviated SERCA2 dysfunction-induced MAM formation and vascular calcification in SKI mice and cultured SKI VSMC, while TSPO overexpression aggravated these effects. Inhibition of the downstream mitochondrial calcium uniporter (MCU) reduced mitochondrial calcium overload and thus alleviated the pro-calcific effects of TSPO in SKI VSMC. In conclusion, SERCA2 dysfunction promotes TSPO-dependent MAM formation, which couples SERCA2 to the IP3R1-Grp75-VDAC1-MCU complex, causing mitochondrial impairment and calcium overload. This study uncovers the pivotal role of SERCA2 during vascular calcification, delineates the novel components of the MAM complex, and highlights potential therapeutic targets of vascular calcification.
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DOI
PubMed
高影响因子
Scientific Reports
·
2026
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IF 4.9
Wang Ke,Liu Huai-yu,Wang Yue,Su Gen-zheng,Gao Jin-lai,Wang Yan-Ping,He Zhi
Mitochondrial calcium homeostasis may offer therapeutic benefits for ischemic stroke. Harpagide has been shown to inhibit mitochondrial calcium uptake, but the mechanism remains unclear. In this study, a male ICR mouse model of permanent middle cerebral artery occlusion (pMCAO)-induced focal cerebral ischemia and PC12 and SH-SY5Y cells exposed to oxygen–glucose deprivation (OGD) were used. Apoptosis, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and the ATP levels were measured to assess the neuroprotective effects of harpagide. DCFH-DA, JC-1, and Rhod-2A probes were used to analyze the mitochondrial function. RT-qPCR and western blot were used to determine the mitochondrial calcium uniporter (MCU), the apoptosis-inducing factor (AIF), Endo G, Cyt C, Caspase-3, and AMPK–MCU phosphorylation expression levels. Additionally, Longa scoring and triphenyl tetrazolium chloride (TTC) staining were used. Transmission electron microscopy (TEM) was used to examine the mitochondrial ultrastructural changes. An immunohistochemical analysis was conducted to detect the MCU expression in the temporal cortex. Harpagide attenuated OGD-induced cytotoxicity, as evidenced by reduced lactate LDH leakage, restored ATP generation, and ameliorated mitochondrial ultrastructural damage. Mechanistically, harpagide suppressed oxidative stress and alleviated mitochondrial calcium ([Ca 2+ ] mito ) overload, concomitant with modulated expression of MCU complex components and apoptosis-related proteins. These neuroprotective effects were linked to harpagide-mediated AMPK expression and subsequent preservation of mitochondrial bioenergetics and calcium homeostasis. Collectively, these findings position harpagide as a promising phytochemical candidate for ameliorating mitochondrial dysfunction in ischemic stroke, warranting further investigation into its precise molecular interactions with the AMPK–MCU axis.
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产品关联
DOI
PubMed
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
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2016
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IF 8.328
Haiping Li,Tingxia Hu,Renjie Zhang,Jianqiang Liu,Wanguo Hou
Up to now, studies on solid-state Z-scheme two-component heterojunctions have hardly referred to roles of interfacial internal electric fields (IEFs). Herein, solid-state Z-scheme Bi 2 MoO 6 /MO (M = Cu, Co 3/4 , or Ni) heterojunction photocatalysts were simply synthesized, for the first time, with enhanced photocatalytic performance toward organic degradation. Electron microscopy images reveal that the MO homogeneously distributes on surfaces of the Bi 2 MoO 6 hierarchical microspheres, and they close contact with distinct heterojunction interfaces. X-ray photoelectron spectra (XPS) suggest that the electron transfer occurs between the Bi 2 MoO 6 and MO after they contact, resulting in formation of IEFs at their interfaces. Based on band gap values and valance-band XPS and ultraviolet photoelectron spectra, energy band levels of the Bi 2 MoO 6 and MO are defined, and directions of the interfacial IEFs are determined. The IEFs play key roles for the formation of the Z-scheme Bi 2 MoO 6 /MO heterojunctions and for the photoactivity enhancement. This work provides a better insight into the formation mechanism of solid-state two-component Z-scheme heterojunctions and a significant experimental guidance for studying other similar systems.
研究领域:
材料科学
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环境科学
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产品关联
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
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2023
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IF 10.9
Jianmao Zheng,Jiyuan Zuo,Cairong Xiao,Qining Guo,Xiaobin Fu,Chengyun Ning,Peng Yu
The induction of dental pulp stem cells (DPSCs) into odontogenic differentiation is a cutting-edge method of dental pulp regeneration treatment. However, it remains a challenge to develop biomaterials and therapies that can induce odontogenic differentiation. Here, we propose a wireless electrical stimulation strategy to induce DPSCs odontogenic differentiation via K 0.5 Na 0.5 NbO 3 piezoelectric nanoparticles (KNN) and polarized KNN (PKNN), which can be endocytosed by DPSCs. In vitro, several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN, and the increase was more obvious in the PKNN group. Intracellular wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter (MCU), increased the production of adenosine triphosphate (ATP), and induced odontogenic differentiation through the activation of the cAMP-PKA signaling pathway. In vivo, dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN, which was more clinically friendly compared with the wired device, and the induction was more obvious in the PKNN group consistent with in vitro experiments. In conclusion, this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.
研究领域:
牙科学
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生物材料
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干细胞生物学
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纳米技术
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再生医学
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY
·
2024
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IF 4.8
Junke Wang,Yuexin Wei,Yuhao Wu,Tianxin Zhao,Lian Kang,Lindong Han,Jiadong Chen,Chunlan Long,Guanghui Wei,Lianju Shen,Shengde Wu
As one of the most prevalent environmental endocrine disruptors, di-(2-ethylhexyl) phthalate (DEHP) is known for its significant developmental toxicity to the male reproductive system in humans and mice. Prepubertal exposure to DEHP has been shown to cause testicular damage, but the underlying mechanisms require further investigation. To investigate this effect, prepubertal mice were exposed to 250 or 500 mg/kg body weight (bw) of DEHP for 14 days, which resulted in impaired histological structure and increased apoptosis of the testes. RNA sequencing (RNA-seq) of testicular tissue suggested that DEHP led to injury in Leydig and Sertoli cells. To further elucidate these mechanisms, we conducted experiments using immature mouse Leydig (TM3) and Sertoli (TM4) cells, and exposed them to 200 μM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP, for 24 h. We found that MEHP exposure induced oxidative stress injury and promoted cell apoptosis, and that cotreatment with N-acetylcysteine partially reversed these injuries. Given the close association between oxidative stress and mitochondrial calcium levels, we demonstrated that MEHP exposure disrupted mitochondria and increased mitochondrial calcium levels. This effect facilitated the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs), upregulated protein expression and enhanced the interactions of the IP3R3-Grp75-VDAC1 complex. Furthermore, inhibition of calcium transfer in the IP3R3-Grp75-VDAC1-MCU axis relieved MEHP-induced mitochondrial injury, oxidative stress and apoptosis in TM3 and TM4 cells. This study highlights the importance of MAM-mediated mitochondrial calcium overload and the subsequent apoptosis of Leydig and Sertoli cells as pivotal factors contributing to testicular injury induced by prepubertal exposure to DEHP.
研究领域:
环境科学
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毒理学
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生殖生物学
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细胞生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Redox Biology
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2021
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IF 11.799
Sufang Shui,Zenglu Zhao,Hao Wang,Marcus Conrad,Guoquan Liu
Ferroptosis is primarily triggered by a failure of the glutathione (GSH)-glutathione peroxidase 4 (GPX4) reductive system and associated overwhelming lipid peroxidation, in which enzymes regulating polyunsaturated fatty acid (PUFA) metabolism, and in particular acyl-CoA synthetase long chain family member 4 (ACSL4), are central. Here, we found that exogenous oxygen radicals generated by photodynamic therapy (PDT) can directly peroxidize PUFAs and initiate lipid autoxidation, coinciding with cellular GSH depletion. Different from canonical ferroptosis induced by RSL3 or erastin, PDT-initiated lipid peroxidation and ferroptotis-like cell death is independent of lipoxygenase (ALOXs) and ACSL4. Especially, this form of cell death modality can be triggered in malignant cells insensitive to or acquired resistance to canonical ferroptosis inducers. We also observed a distinct iron metabolism pathway in this PDT-triggered cell death modality, in which cytosolic labile iron is decreased probably due to its relocation to mitochondria. Inhibition of the mitochondrial Ca 2+ and Fe 2+ uniporter (MCU) effectively prevented PDT-triggered lipid peroxidation and subsequent cell death. Therefore, we tentatively term this distinct ferroptosis-like cell death as liperoptosis. Moreover, using the clinically approved photosensitizer Verteporfin, PDT inhibited tumor growth through inducing prevailing ferroptosis-like cell death in a mouse xenograft model. With its site-specific advantages, these findings highlight the value of using PDT to trigger lipid peroxidation and ferroptosis-like cell death in vivo , and will benefit exploring the exact molecular mechanism of immunological effects of PDT in cancer treatment.
研究领域:
肿瘤学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
·
2019
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IF 3.067
Yonghong Miao,Xiaoxue Sun,Guojun Gao,Xianglei Jia,Hao Wu,Ying Chen,Liyong Huang
(-)-epigallocatechin-3-gallate (EGCG), the main component of green tea, has long been explored in the treatment and/or prevention of central nervous system (CNS) disorders. However, EGCG has been recently shown to exhibit acute and subacute toxicity. Although a lot of work has been done, the mechanisms of EGCG-induced mitochondrial dysfunction has not been delineated in primary astrocyte. Here, the mitotoxic effect of EGCG on primary astrocytes was investigated by measuring Ca 2+ overloading-induced mitochondrial dysfunction. As expected, EGCG dose-dependently inhibited astrocytes growth depending on Ca 2+ overloading, especially at 50 μM EGCG group. It is interesting to note that Ca 2+ influx from the extracellular space was responsible for an increase in the cytosolic Ca 2+ level ([Ca 2+ ] i ) by opening voltage-gated calcium channels (VGCCs) and, consequently, mitochondrial Ca 2+ ([Ca 2+ ] m ) overloaded via the mitochondrial Ca 2+ uniporter (MCU). As a result, mitochondrial dysfunction was induced, including the opening of the mitochondrial permeability transition pore (mPTP), mitochondrial membrane depolarization, an increasing in reactive oxygen species (ROS), and cytochrosome c (cyt c) releasing. Therefore, more apoptotic cells were observed in 50 μM EGCG group than that of in 1 μM EGCG group. These findings suggested that a high dose of EGCG was toxic to astrocytes partly by targeting mitochondria via calcium pathway, which would extend our understanding of the toxicity of EGCG and the underlying mechanisms.
研究领域:
神经科学
·
药理学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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