MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Chaoqun Fei,Shulan Qi,Jiahuan Zhang,Shi Zhou,Yingxue Guo,Yanli Zhao,Jiazheng Jin,Jinlian Li,Ximing Cui,Dongmei Wu
As industrialization accelerates, there is an increasing need to find a quick, easy, and affordable method to assess the potential DNA damage caused by newly developed chemicals. Electrochemical voltammetry using intracellular purine bases as markers shows promise for detecting DNA damage. However, it is unclear whether drugs with different DNA damage mechanisms will impact purine metabolism in cells and consequently disturb the electrochemical indicators of DNA damage. In this paper, the electrochemical behaviors of HepG2 cells exposed to the direct DNA-damaging agent (MNNG), the indirect DNA-damaging agent (CPT11), and the non-DNA-damaging agent (KCl) were studied. The findings showed that the electrochemical signals of cells increased with the rising concentration of DNA-damaging drugs. A time-dependent effect was observed, with a lower threshold dose for 4 h compared to 1 h. However, the non-DNA-damaging agent did not induce an increase in the cellular electrochemical signal. Despite the higher cytotoxicity of CPT11, MNNG triggered DNA damage at a lower dose, as detected by electrochemical indicators. The results of the electrochemical indicators assessment of DNA damage correlated significantly with those of the γH2AX focus and alkaline comet assays, with r > 0.98 and P < 0.01. Particularly, there was a stronger correlation with the alkaline comet assay. Furthermore, electrochemical voltammetry detected DNA damage at a lower threshold compared to other assessment methods, demonstrating a higher sensitivity to DNA damage. These findings suggest that by using purine bases as markers, electrochemical voltammetry enables precise assessment of DNA damage caused by various mechanisms.
研究领域:
毒理学
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药理学
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分子生物学
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生物医学工程
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产品关联
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2017
·
IF 2.313
Sen Zhang,Huan Chen,An Wang,Yong Liu,Hongwei Hou,Qingyuan Hu
To evaluate the genotoxic effects of formaldehyde, acetaldehyde, acrolein and benzene on A549 cells, the in vitro γH2AX assay was used in combination with high content screening (HCS) technology. All aldehydes showed a significant genotoxicity in a dose/time-dependent effect on the induction of γH2AX. Benzene failed to show a significant genotoxicity based on the γH2AX assay. However, hydroquinone (one of metabolites of benzene) showed a significant genotoxicity in vitro. Based on the dose-response of γH2AX and Hill model, the ability to induce DNA double-strand break can be evaluated as acrolein > formaldehyde > acetaldehyde > benzene. The slow DNA damage/repair mechanism may be more important than the fast one for aldehydes based on time-course of γH2AX and two-component model. Overall, all toxicants were genotoxic in a dose- or time-dependent manner based on the in vitro γH2AX HCS assay, and acrolein had a strong potential to induce DNA damage followed by formaldehyde, acetaldehyde and benzene in sequence.
研究领域:
毒理学
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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
Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology
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2016
·Vol. 299
·期 4
·450-460
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IF 1.507
Fuyin Hou,Min Xiao,Jian Li,Devin W. Cook,Weidong Zeng,Caiqiao Zhang,Yuling Mi
Cadmium (Cd) is an environmental endocrine disruptor that has toxic effects on the female reproductive system. Here the ameliorative effect of grape seed proanthocyanidin extract (GSPE) on Cd-induced meiosis inhibition during oogenesis was explored. As compared with controls, chicken embryos exposed to Cd (3 µg/egg) displayed a changed oocyte morphology, decreased number of meiotic germ cells, and decreased expression of the meiotic marker protein γH2AX. Real time RT-PCR also revealed a significant down-regulation in the mRNA expressions of various meiosis-specific markers ( Stra8 , Spo11 , Scp3 , and Dmc1 ) together with those of Raldh2 , a retinoic acid (RA) synthetase, and of the receptors ( RARα and RARβ ). In addition, exposure to Cd increased the production of H 2 O 2 and malondialdehyde in the ovaries and caused a corresponding reduction in glutathione and superoxide dismutase. Simultaneous supplementation of GSPE (150 µg/egg) markedly alleviated the aforementioned Cd-induced embryotoxic effects by upregulating meiosis-related proteins and gene expressions and restoring the antioxidative level. Collectively, the findings provided novel insights into the underlying mechanism of Cd-induced meiosis inhibition and indicated that GSPE might potentially ameliorate related reproductive disorders. Anat Rec, 299:450–460, 2016. © 2016 Wiley Periodicals, Inc.
研究领域:
毒理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Redox Biology
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2023
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IF 11.4
Chen-Yu Zhang,Wen-Jing Zhong,Yu-Biao Liu,Jia-Xi Duan,Nan Jiang,Hui-Hui Yang,Sheng-Chao Ma,Ling Jin,Jie-Ru Hong,Yong Zhou,Cha-Xiang Guan
Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro , we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and γH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.
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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呼吸医学
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DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
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2020
·Vol. 295
·期 20
·6958-6971
·
IF 4.238
Chunyan Liao,Binxiang Cai,Yufeng Feng,Jingmeng Chen,Yiping Wu,Jingbin Zhuang,Zuguo Liu,Yalin Wu
Disrupted clearance of all-trans-retinal (atRAL), a component of the visual (retinoid) cycle in the retina, may cause photoreceptor atrophy in autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD). However, the mechanisms underlying atRAL-induced photoreceptor loss remain elusive. Here, we report that atRAL activates c-Jun N-terminal kinase (JNK) signaling at least partially through reactive oxygen species production, which promoted mitochondria-mediated caspase- and DNA damage-dependent apoptosis in photoreceptor cells. Damage to mitochondria in atRAL-exposed photoreceptor cells resulted from JNK activation, leading to decreased expression of Bcl2 apoptosis regulator (Bcl2), increased Bcl2 antagonist/killer (Bak) levels, and cytochrome c (Cyt c) release into the cytosol. Cytosolic Cyt c specifically provoked caspase-9 and caspase-3 activation and thereby initiated apoptosis. Phosphorylation of JNK in atRAL-loaded photoreceptor cells induced the appearance of γH2AX, a sensitive marker for DNA damage, and was also associated with apoptosis onset. Suppression of JNK signaling protected photoreceptor cells against atRAL-induced apoptosis. Moreover, photoreceptor cells lacking Jnk1 and Jnk2 genes were more resistant to atRAL-associated cytotoxicity. The Abca4−/− Rdh8−/− mouse model displays defects in atRAL clearance that are characteristic of STGD1 and dry AMD. We found that JNK signaling was activated in the neural retina of light-exposed Abca4−/−Rdh8−/− mice. Of note, intraperitoneal administration of JNK–IN-8, which inhibits JNK signaling, effectively ameliorated photoreceptor degeneration and apoptosis in light-exposed Abca4−/−Rdh8−/− mice. We propose that pharmacological inhibition of JNK signaling may represent a therapeutic strategy for preventing photoreceptor loss in retinopathies arising from atRAL overload.
研究领域:
眼科学
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细胞生物学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
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