Food & Function
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2018
·Vol. 9
·期 12
·6349-6359
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IF 3.289
Ying Chen,Jianjun Chen,Xiaoxue Sun,Xiaoxiao Shi,Lei Wang,Liyong Huang,Wenke Zhou
(−)-Epigallocatechin-3-gallate (EGCG), the main bioactive component of tea catechins, exhibits broad-spectrum health efficacy against mitochondrial damage after subarachnoid hemorrhage (SAH). The mechanisms, however, are largely unknown. Here, the ability of EGCG to rescue mitochondrial dysfunction and mitochondrial dynamics following the inhibition of cell death was investigated by using in vitro and in vivo SAH models. EGCG blocked the cytosolic channel ([Ca2+])i influx via voltage-gated calcium channels (VGCCs), which induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) release. As expected, EGCG ameliorated oxyhemoglobin (OxyHb)-induced impairment of mitochondrial dynamics by regulating the expression of Drp1, Fis1, OPA1, Mfn1, and Mfn2. As a result, EGCG restored the increases in fragmented mitochondria and the mtDNA copy number in the OxyHb group to almost the normal level after SAH. In addition, the normal autophagic flux induced by EGCG at both the initiation and formation stages regulated Atg5 and Beclin-1 after SAH for the timely elimination of damaged mitochondria. In the end, EGCG increased the neurological score by decreasing cell death through the cyt c-mediated intrinsic apoptotic pathway. The results revealed the mechanisms behind the neuroprotective effects of EGCG via inhibition of the overloaded [Ca2+]i-induced mitochondrial dysfunction and the imbalanced mitochondrial fusion and fission cycle. Therefore, the simultaneous inhibition and timely elimination of damaged mitochondria could determine the therapeutic effect of EGCG.
研究领域:
神经保护
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线粒体生物学
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神经病学
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药理学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
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2019
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IF 3.499
Lingmin Zhang,Qingqing Xia,Yingying Zhou,Jie Li
Excessive accumulation of cadmium (Cd) in retina plays an important role in tobacco smoking-associated age-related macular degeneration (AMD). Plenty of evidence has revealed that the retinal pigment epithelium (RPE) is the primary site of pathology in AMD. Our current study demonstrated that Cd induced apoptosis in a human RPE cell line ARPE-19 cells, as it dose-dependently caused cell viability loss and activated caspase-3. The reactive oxygen species (ROS) were confirmed to be important mediators for Cd-triggered cell death in ARPE-19 cells. We found that endoplasmic reticulum (ER) stress was activated as its marker BiP was remarkably upregulated by Cd-exposure. Whereas the antioxidants N-acetylcysteine (NAC) and Tempol significantly suppressed the expression of BiP and CHOP, suggesting that ROS generation is an early trigger of Cd-activated ER stress. Furthermore, we found that Cd-induced oxidative stress significantly increased autophagic flux and p62 expression. A temporal impact of Cd exposure is possibly existed in p62 expression in ARPE-19 cells. Moreover, an ER stress inhibitor salubrinal diminished Cd-induced LC3BII expression and attenuated cytotoxicity, indicating that ER stress mediates autophagy and was implicated in apoptosis of Cd-exposed ARPE-19 cells. However, CHOP expression may not exert impact on the regulation of Cd-caused autophagy. Additionally, inhibition of autophagy with si-Beclin 1 and 3-Methyladenine significantly ameliorated Cd-induced CHOP expression and cytotoxicity, indicating that autophagy was detrimental in Cd-accumulated ARPE-19 cells, and a positive feedback regulation mechanism may exist between Cd-triggered ER stress and autophagy. Taken together, these results suggest that Cd-caused ER stress and autophagy are implicated in RPE cell death associated retinopathies especially related to smoking.
研究领域:
毒理学
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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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DOI
PubMed
高影响因子
LIFE SCIENCES
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2017
·
IF 2.936
En-Xia Wang,Bo-Yang Zou,Lei Shi,Lin-Ying Du,Yan-Yan Zhu,Ya-Meng Jiang,Xiao-Dong Ma,Xiao-Hui Kang,Chang-Yuan Wang,Yu-Hong Zhen,Li-Dan Sun
Aims To investigate the antitumor effects of 7- O -geranylquercetin (GQ), a novel O -alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms. Main methods Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay. Cell cycle and reactive oxygen species (ROS) level were detected using flow cytometry. Key findings GQ inhibited viability of A549 and NCI-H1975 cells in a dose- and time-dependent manner without apparent cytotoxicity to normal human lung fibroblast cells. GQ down-regulated the expression of apoptosis-related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation of ROS, and ROS inhibitor N -acetylcysteine could reverse GQ-induced autophagy and apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to apoptosis. Significance Our findings highlight that GQ is a promising anticancer agent for the treatment of lung cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
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2021
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IF 4.076
Lihua Li,Jun Chen,Yun Zhou,Jiahua Zhang,Lei Chen
Context Artesunate (ART), an antimalarial drug, possesses the ability to induce autophagy and exhibits a protective effect on diabetes.Objective This study aimed to evaluate the effects of ART on diabetic retinopathy (DR) and to explore the underlying mechanisms.Methods Rats with streptozotocin-induced DR were given intravitreal injection of ART.Results ART administration inhibited the increase in retinal thickness and prevented blood–retinal barrier in diabetic rats. Further, vascular leukocyte adherence, microglial activation, inflammatory cytokine, and ROS production in the retinas of diabetic rats were also inhibited by ART. Additionally, ART enhanced autophagy in the retinas of diabetic rats as demonstrated by up-regulated Beclin-1 expression and LC3II/I ratio and down-regulated p62. ART also activated AMP-activated protein kinase (AMPK)/sensor class III histone deacetylase sirtuin 1 (SIRT1) pathway.Conclusions ART, as an autophagy activator, has therapeutic potential in DR treatment.
研究领域:
药理学
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眼科学
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糖尿病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Kun Hu,Shaojun Wu,Jiaxin Xu,Yongzhen Zhang,Yanan Zhang,Xinyuan Wu,Jie Miao,Yongxu Yao,Susu Zhu,Guangtong Chen,Jie Ren
Alzheimer’s disease (AD), one of the neurodegenerative disorders, is highly correlated with the abnormal hyperphosphorylation of Tau and aggregation of β-amyloid (Aβ). Oxidative stress, neuroinflammation, and abnormal autophagy are key drivers of AD and how they contribute to neuropathology remains largely unknown. The flavonoid compound pongamol is reported to possess a variety of pharmacological activities, such as antioxidant, antibacterial, and anti-inflammatory. This study investigated the neuroprotective effect and its mechanisms of pongamol in lipopolysaccharide (LPS)-induced BV2 cells, d-galactose/sodium nitrite/aluminum chloride (d-gal/NaNO2/AlCl3)-induced AD mice, and Caenorhabditis elegans models. Our research revealed that pongamol reduced the release of inflammatory factors IL-1β, TNF-α, COX-2, and iNOS in LPS-induced BV2 cells. Pongamol also protected neurons and significantly restored memory function, inhibited Tau phosphorylation, downregulated Aβ aggregation, and increased oxidoreductase activity in the hippocampus of AD mice. In addition, pongamol reversed the nuclear transfer of NF-κB and increased the levels of Beclin 1 and LC3 II/LC3 I. Most importantly, the anti-inflammatory and promoter autophagy effects of pongamol may be related to the regulation of the Akt/mTOR signaling pathway. In summary, these results showed that pongamol has a potential neuroprotective effect, which greatly enriched the research on the pharmacological activity of pongamol for improving AD.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2017
·Vol. 17
·期 1
·158-164
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IF 1.692
Yang‑Hua Tang,Zhen‑Shuang Yue,Guo‑Song Li,Lin‑Ru Zeng,Da‑Wei Xin,Zhong‑Qing Hu,Can‑Da Xu
The aim of the present study was to investigate the effect of glucocorticoids in osteoblasts and to examine the role of β‑ecdysterone in the pathogenesis of glucocorticoid‑induced osteoporosis. Osteoblasts were induced from bone marrow mesenchymal stem cells, which were isolated from C57BL/6 mice. Cell viability and apoptosis of osteoblasts were measured by Cell Counting Kit‑8 and flow cytometry analysis, respectively. The expression of related genes and proteins was measured by reverse transcription quantitative polymerase chain reaction and western blot analysis respectively. Dose‑dependent decreases in the cell proliferation and differentiation were observed in dexamethasone (Dex)‑treated osteoblasts, evidenced by downregulation in the activity of alkaline phosphatasedecreased expression levels of Runt‑related transcription factor 2 and osteocalcin, and upregulated expression of RANK ligand. Dex also induced apoptosis and inhibited autophagy of osteoblasts, evidenced by upregulated B‑cell lymphoma 2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio and the activation of mammalian target of rapamycin (mTOR), and decreased expression levels of Beclin‑1, autophagy protein 5 and microtubule‑associated protein 1 light chain 3 II. The effects on cell proliferation, apoptosis and autophagy induced by Dex were reversed by β‑ecdysterone in a dose‑dependent manner. Therefore, β‑ecdysterone may be a promising candidate drug for the treatment of osteoporosis through inducing osteoblast autophagic activity by inactivating mTOR.
研究领域:
药理学
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骨科
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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