Cell Death Discovery
·
2021
·Vol. 7
·期 1
·1-10
·
IF 5.241
Bian Wan-Ping,Pu Shi-Ya,Xie Shao-Lin,Wang Chao,Deng Shun,Strauss Phyllis R.,Pei De-Sheng
MVP17 encodes a mitochondrial inner-membrane protein, and mutation of human MVP17 can cause mitochondria DNA depletion syndrome (MDDS). However, the underlying function of mpv17 is still elusive. Here, we developed a new mutant with mpv17 knockout by using the CRISPR/Cas9 system. The mpv17 −/− zebrafish showed developmental defects in muscles, liver, and energy supply. The mpv17 −/− larvae hardly survived beyond a month, and they showed abnormal growth during the development stage. Abnormal swimming ability was also found in the mpv17 −/− zebrafish. The transmission electron microscope (TEM) observation indicated that the mpv17 −/− zebrafish underwent severe mitochondria dysfunction and the disorder of mitochondrial cristae. As an energy producer, the defects of mitochondria significantly reduced ATP content in mpv17 −/− zebrafish, compared to wild-type zebrafish. We hypothesized that the disorder of mitochondria cristae was contributed to the dysfunction of muscle and liver in the mpv17 −/− zebrafish. Moreover, the content of major energy depot triglycerides (TAG) was decreased dramatically. Interestingly, after rescued with normal exogenous mitochondria by microinjection, the genes involved in the TAG metabolism pathway were recovered to a normal level. Taken together, this is the first report of developmental defects in muscles, liver, and energy supply via mitochondria dysfunction, and reveals the functional mechanism of mpv17 in zebrafish.
研究领域:
发育生物学
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分子遗传学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2025
·
IF 3.3
Liping Lu,kang chunyu
Nicotinamide adenine dinucleotide (NADH) is a crucial biomolecule that serves as an essential cofactor in numerous biocatalytic reactions and a pivotal regulator of mitochondrial function and cellular physiology. This study developed a SECM platform utilizing a double-mediator system for the real-time, in situ, and non-invasive detection of intracellular NADH at the single living cell level. The system employs 1-methoxy-5-methylphenazinium methyl sulfate (mPMS), which permeates the cell membrane to oxidize intracellular NADH, and ferricyanide ([Fe(CN)₆]³⁻), which shuttles electrons from the reduced mPMS to the SECM tip. This methodology was applied to investigate mitochondrial impairment in human hepatoma (HepG2) cells induced by polycyclic aromatic sulfur heterocycles (PASHs). The metabolic response was corroborated by analyzing poly(ADP-ribose) polymerase (PARP) activity, adenosine triphosphate (ATP) content, and mitochondrial membrane potential (MMP). Results demonstrated that exposure to dibenzothiophene (DBT) activated PARP, leading to severe depletion of NADH and ATP and a significant decline in MMP, thereby confirming comprehensive mitochondrial dysfunction. Comparative analysis with its non-sulfur analog fluorene (Flu) revealed that the sulfur atom in DBT's structure is a critical determinant of its enhanced cytotoxicity. This work establishes a reliable and innovative analytical approach for assessing the subcellular metabolic effects of environmental pollutants, providing a new platform for in-depth cytotoxicity mechanistic studies.
研究领域:
分析生物医学
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环境毒理学
·
细胞代谢
·
分子毒理学
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肿瘤学
·
生物电化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Mengwen Li,Yue Tian,Xiaoming Wen,Jingke Fu,Jianyong Gao,Yingchun Zhu
The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable meso-organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The meso-organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Wei Shi,Yu Han,Shuge Sun,Yu Tang,Weishang Zhou,Xueying Du,Guangxu Liu
Although coexposure to pharmaceuticals and microplastics (MPs) may frequently occur, the synergistic impact of MPs and antidepressants on marine species still remains poorly understood. In this study, the immunotoxicities of polystyrene MPs (diameters 500 nm and 30 μm) and sertraline (Ser), alone and in combination, were investigated in a bivalve mollusk Tegillarca granosa . Results showed that both MPs and Ser significantly suppressed the immune responses of T. granosa . In addition, though the toxic effect of Ser was not affected by microscale MPs, an evident synergistic immuno-toxic effect was observed between Ser and nanoscale MPs, which indicates a size-dependent interaction between the two. To further ascertain the underlying toxication mechanisms, the intracellular content of reactive oxygen species , apoptosis status, ATP content, pyruvate kinase activity, plasma cortisol level, and in vivo concentrations of neurotransmitters and cytochrome P450 1A1 were analysed. A transcriptomic analysis was also performed to reveal global molecular alterations following Ser and/or MPs exposure. The obtained results indicated that the presence of nanoscale MPs may enhance the immunotoxicity of Ser by (i) inducing apoptosis of haemocytes and, hence, reducing the THC; (ii) constraining the energy availability for phagocytosis; and (iii) hampering the detoxification of Ser.
研究领域:
环境科学
·
毒理学
·
海洋生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 4
·2149-2161
·
IF 6.1
Ai-Wen Kang,Chi Sun,Hai-Tao Li,Kun Zhong,Xu-Hui Zeng,Zhi-Feng Gu,Bing-Qian Li,Xiao-Ning Zhang,Jian-Lin Gao,Tian-Xing Chen
Lifespan longevity has attracted increasing attention with societal development. To counter the effects of aging on longevity, we focused on the natural chemicals of plants. In this study, we investigated the effects of puerarin supplementation on the lifespan of Drosophila melanogaster. Puerarin supplementation significantly extended the lifespan of D. melanogaster at 60 μM and 120 μM by upregulating proteasome subunit beta 5 (prosbeta5) and sirtuin-1 (Sirt1). However, puerarin-induced longevity of male flies (F0 generation) may not be passed on to descendants. Additionally, a puerarin diet for 10 and 25 days did not influence the body weight and food intake of male Canton-S flies. Puerarin significantly improved the climbing ability, starvation resistance, and oxidation resistance of male flies by upregulating the expression of Shaker, catalase (CAT), superoxide dismutase 1 (SOD1), and Methuselah, and downregulating poly [ADP-ribose] polymerase (PARP-1) and major heat shock 70 kDa protein Aa (HSP70). Moreover, 120 μM puerarin supplementation for 25 days significantly increased adenosine 5′ triphosphate (ATP) content by increasing adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) levels. Additionally, the puerarin diet for 25 days suppressed male fecundity in male flies by decreasing the levels of Bam and Punt. Mechanistically, puerarin enhanced lysosome-involved autophagy by promoting the expression of lysosome markers [β-galactosidase and lysosomal associated membrane protein 1 (LAMP1)], and elevating the levels of autophagy-related genes, including autophagy-associated gene 1 (ATG1), ATG5, and ATG8b. However, puerarin decreased the phosphorylation of the target of rapamycin (TOR) protein. In conclusion, puerarin is a promising compound for improving the longevity of D. melanogaster by activating autophagy.
研究领域:
衰老研究
·
药理学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2019
·
IF 7.149
Wei Guo,Jian Han,Shengmin Wu,Xiongjie Shi,Qiangwei Wang,Bingsheng Zhou
Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is a ubiquitous environmental contaminant, but its toxicity is not fully understood. Accordingly, we investigated the effects of TBPH and its metabolite, mono-(2-ethyhexyl)tetrabromophthalate (TBMEHP), on lipid metabolism using a zebrafish model. The molecular docking study revealed that TBPH and TBMEHP bind to zebrafish peroxisome proliferator-activated receptor γ (PPARγ), with binding energies similar to rosiglitazone, a PPARγ agonist. Zebrafish embryos 0.75 hpf were exposed to TBPH (0.2–2000 nM) or TBMEHP (0.2–2000 nM) until 72 hpf, and their effects on PPARγ-mediated lipid metabolism were evaluated. Significant regional DNA demethylation of the PPARγ promoter was observed in the larvae at 72 hpf. Demethylation of the PPARγ promoter accompanied by upregulation of tet1 and tet2 transcription caused upregulation of PPARγ transcription and certain downstream genes involved in lipid lipolysis, transport, and metabolism. The triglyceride and total cholesterol concentrations in the larvae were significantly reduced following exposure to TBPH or TBMEHP. Furthermore, significant increases in the whole ATP content and locomotor activity in the 120 hpf larvae were observed. The overall results suggest that both TBPH and TBMEHP affect methylation of the PPARγ promoter, subsequently influencing larvae lipid metabolism via the PPARγ signaling pathway and disrupting energy homeostasis.
研究领域:
环境毒理学
·
分子生物学
·
发育生物学
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2024
·
IF 6.4
Qiuxiao Yang,Dingding Shi,Yanling Ren,Chao Yang,Hongxia Qu,Yueming Jiang,Taotao Li
Pericarp browning is a vital factor limiting postharvest life of litchi fruit. The influence of vitexin on pericarp browning as well as the related mechanisms in litchi fruit were investigated. Results demonstrated that 1 mM vitexin ameliorated pericarp browning when litchi fruit were stored at 25 °C. Meanwhile, vitexin blocked reactive oxygen species (ROS) production but increased the glutathione peroxidase activity, thereby playing a protective role in oxidative injury. Additionally, vitexin attenuated ATP content decline in relation to regulation of LcSnRK1 as well as LcbZIP1/3 expressions. Furthermore, vitexin regulated expression levels of autophagy-related genes. Finally, LcbZIP3 activated the expressions of LcATG2 and Lcbeclin-1-like protein based on dual-luciferase report (DLR) assay. This is the first report that confers vitexin-meditated protective role in delaying litchi pericarp browning that could be linked to its effects on autophagy particularly regulated via LcSnRK1a–LcbZIP1/3 signaling pathway. Vitexin treatment might be an effective approach to control postharvest senescence of fruit during storage.
研究领域:
植物科学
·
采后生理学
·
分子生物学
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产品关联
DOI
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-11
·
IF 4.259
Zhao Hongting,Li Huihui,Hao Shuangying,Chen Jiping,Wu Jing,Song Chuanhui,Zhang Meng,Qiao Tong,Li Kuanyu
Friedreich ataxia is a progressive neurodegenerative disease caused by the expansion of GAA trinucleotide repeats within the first intron of the FXN gene, which encodes frataxin. The pathophysiology of the disease is thought to be derived from the decrease of Fe-S cluster biogenesis due to frataxin deficiency. There is currently no effective treatment for the disease. In our study, we demonstrated that treatment with the mitochondrion-targeted peptide SS-31 reduced frataxin deficiency-induced oxidative stress in lymphoblasts and fibroblasts derived from patients. Interestingly, SS-31 treatment translationally upregulated the protein level of frataxin in a dose-dependent manner. Furthermore, SS-31 treatment increased the enzymatic activities of the iron-sulphur enzymes, including aconitase and complex II and III of the respiratory chain. Further evaluation of the quality of mitochondria showed that mitochondrial membrane potential, ATP content, NAD + /NADH, and the morphology of mitochondria all improved. Our results suggest that SS-31 might potentially be a new drug for the early treatment of Friedreich ataxia.
研究领域:
神经退行性疾病
·
分子生物学
·
线粒体生物学
·
遗传病
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Miaolin Zeng,Huifen Zhou,Yu He,Haixia Du,Junjun Yin,Yongchun Hou,Jiaqi Zhu,Yangyang Zhang,Chongyu Shao,Jiehong Yang,Haitong Wan
Mannitol, a representative of hyperosmolar therapy, is indispensable for the treatment of malignant cerebral infarction, but its therapeutic effect is limited by its exacerbation of blood-brain barrier (BBB) disruption. This study was to explore whether Danhong injection (DHI), a standardized product extracted from Salvia miltiorrhiza Bunge and Carthamus tinctorius L ., inhibits the destructive effect of mannitol on BBB and thus enhancing the treatment of hemispheric ischemic stroke. SD rats were subjected to pMCAO followed by intravenous bolus injections of mannitol with/without DHI intervention. Neurological deficit score, brain edema, infarct volume at 24 h after MCAO and histopathology, microvascular ultrastructure, immunohistochemistry and immunofluorescence staining of endothelial cell junctions, energy metabolism in the ischemic penumbra were assessed. Intravenous mannitol after MCAO resulted in a decrease in 24 h mortality and cerebral edema, whereas no significant benefit on neurological deficits, infarct volume and microvascular ultrastructure. Moreover, mannitol led to the loss of endothelial integrity, manifested by the decreased expression of occludin, junctional adhesion molecule-1 (JAM-1) and zonula occluden-1 (ZO-1) and the discontinuity of occludin staining around the periphery of endothelial cells. Meanwhile, after mannitol treatment, energy-dependent vimentin and F-actin, ATP content, and ATP5D expression were down-regulated, while MMP2 and MMP9 expression increased in the ischemic penumbra. All the insults after mannitol treatment were attenuated by addition of intravenous DHI. The results suggest DHI as a potential remedy to attenuate mannitol-related BBB disruption, and the potential of DHI to upregulate energy metabolism and inhibit the activity of MMPs is likely attributable to its effects observed.
研究领域:
神经学
·
药理学
·
中风研究
·
血管生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Yiheng Jin,Haochun Shi,Yanbin Zhao,Jiayin Dai,Kun Zhang
As a new class of organophosphate ester, cresyl diphenyl phosphate (CDP) has been widely monitored in environmental matrices and human samples, nonetheless, its toxicity is not fully understood. Here we described an in-depth analysis of the disruptions in lipid homeostasis of zebrafish following exposure to CDP concentrations ranging from 2.0 to 313.0 μg/L. Nile red staining revealed significant alterations in lipid contents in 72 hpf zebrafish embryos at CDP concentrations of 5.3 μg/L and above. Lipidomic analysis unveiled substantial disruptions in lipid homeostasis. Notably, disruptive effects were detected in various lipid classes, including phospholipids (i.e. cardiolipin, lysophosphatidylcholine, and phosphatidylethanolamine), glycerolipids (triglycerides), and fatty acids (fatty acids (FA) and wax esters (WE)). These alterations were further supported by transcriptional changes, with remarkable shifts observed in genes associated with lipid synthesis, transport, and metabolism, encompassing phospholipids, glycerolipids, fatty acids, and sphingolipids. Furthermore, CDP exposure elicited a significant elevation in ATP content and swimming activity in embryos, signifying perturbed energy homeostasis. Taken together, the present findings underscore the disruptive effects of CDP on lipid homeostasis, thereby providing novel insights essential for advancing the health risk assessment of organophosphate flame retardants .
研究领域:
环境毒理学
·
发育生物学
·
生物化学
·
分子生物学
✓ 已验证
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）