PeerJ
·
2024
·
IF 2.3
Zhaohong Wang,Hui Chen,Xufan Cai,Heqi Bu,Shengzhang Lin
Background Andrographolide (Andro), an extract of Andrographis paniculate (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear. Methods The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through in vitro experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy. Results Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both in vitro and in vivo . The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro. Conclusion Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Caiqi Xu,Yaoyao Wu,Sui Yang,Xuechun Zhao,Hao Zhang,Yunwen Yan,Jiemin Zhao,Wei Wei,Qian Meng,Yujuan Wang,Rui Zhang
DJ-1, also known as PARK7 (Parkinson's disease protein 7), which is involved in cell viability, apoptosis, transcriptional regulation, and oxidative stress adaptation, is also involved in the pathogenesis of various human diseases including carcinogenesis. Here, we aimed to determine the novel mechanism by which DJ-1 inhibition suppresses tumor growth. Our results showed that DJ-1 knockdown in cancer cells promoted the secretion of a significantly larger amount of mitochondrial transcription factor A (TFAM) into the cell culture medium. DJ-1 knockdown promotes p53 translocation to the mitochondria and stimulates the intrinsic mitochondrial apoptosis pathway, resulting in TFAM release. Moreover, DJ-1 knockdown induced the downregulation of sirtuin 3 (SIRT3), which increased the acetylation of TFAM and triggered its release. Furthermore, we found that extracellular TFAM played a critical role in antitumor activity by upregulating the expression of chemokine (C C motif) ligand 4 (CCL4) and chemokine (C-X-C motif) ligand 5 (CXCL5) in cancer cells, contributing to the promotion of M1 macrophage polarization in the tumor microenvironment (TME). Finally, we confirmed that the DJ-1 inhibitor suppressed tumor growth by increasing TFAM release from cancer cells and M1 macrophage polarization in vivo. These findings indicate that the depletion of DJ-1 stimulates apoptosis-dependent TFAM secretion that triggers M1 macrophage polarization, indicating a new therapeutic strategy by interfering with the DJ-1 function in cancer therapy.
研究领域:
肿瘤学
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免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2020
·Vol. 11
·期 1
·1-15
·
IF 12.121
Cao Ji,Chen Xiaobing,Jiang Li,Lu Bin,Yuan Meng,Zhu Difeng,Zhu Hong,He Qiaojun,Yang Bo,Ying Meidan
Ferroptosis is a newly characterized form of regulated cell death mediated by iron-dependent accumulation of lipid reactive oxygen species and holds great potential for cancer therapy. However, the molecular mechanisms underlying ferroptosis remain largely elusive. In this study, we define an integrative role of DJ-1 in ferroptosis. Inhibition of DJ-1 potently enhances the sensitivity of tumor cells to ferroptosis inducers both in vitro and in vivo. Metabolic analysis and metabolite rescue assay reveal that DJ-1 depletion inhibits the transsulfuration pathway by disrupting the formation of the S-adenosyl homocysteine hydrolase tetramer and impairing its activity. Consequently, more ferroptosis is induced when homocysteine generation is decreased, which might be the only source of glutathione biosynthesis when cystine uptake is blocked. Thus, our findings show that DJ-1 determines the response of cancer cells to ferroptosis, and highlight a candidate therapeutic target to potentially improve the effect of ferroptosis-based antitumor therapy.
研究领域:
癌症生物学
·
细胞代谢
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2024
·
IF 4
Rui Liu,Man Qin,Keyue Li,Hai Yu,Mangang Wu,Wenbin Bao,Qingfeng Ge
Reactive oxygen species (ROS) have been recognized to have a significant impact on meat quality, while the role of the antioxidant system in response to ROS in postmortem muscle remain unclear. Protein DJ-1 serves as a sensor of oxidative stress and has an antioxidant function in biological systems. Hence, this study aimed to investigate the expression, oxidation, and interaction of protein DJ-1 in porcine longissimus thoracis (LT) and semimembranous (SM) muscles, as well as its correlation with meat quality, to gain a better understanding of meat quality formation during postmortem aging. The findings indicated significant variations in pH, L* , a* , purge loss, cooking loss, and Warner-Bratzler shear force (WBSF) between the muscle groups ( P < 0.05). The levels of reactive oxygen species (ROS), protein DJ-1, and oxidized DJ-1 (oxDJ-1) in SM muscle were higher than those in LT muscle throughout the 3 d of postmortem aging ( P < 0.05). Moreover, protein DJ-1 and oxDJ-1 were significantly associated with water holding capacity and a* value of pork ( P < 0.05). Through co-immunoprecipitation and mass spectrometry, a total of 23 DJ-1 interacting proteins were identified, mainly participating in glycolysis, energy metabolism, muscle contraction, resistance to oxidative stress, as well as amino acids biosynthesis and metabolism. These results suggest that DJ-1 may exert a regulatory influence on the development of pork quality during postmortem aging.
研究领域:
肉类科学
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宰后生化
·
肌肉生理
·
氧化应激生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 5.2
Jianan Zhang,Yangli He,Yundi Wu,Tian Xie,Wanmeng Fu,Xilong Wu,Lei Zhou,Min Zeng
Effective management of myocardial ischemia/reperfusion (I/R) injury remains a clinical challenge. Epigallocatechin gallate (EGCG), a natural antioxidant, exhibits therapeutic potential in I/R models; however, it is limited by poor bioavailability and inadequate targeted delivery. Therefore, using a synergistic therapeutic strategy, we designed a nanoplatform (PB@PEI@FPBA-EGCG NPs, referred to as PPFE NPs) to address these limitations. PPFE NPs integrate Prussian blue nanoparticles (PB NPs) with EGCG, harnessing the multi-enzyme–mimicking activities of PB NPs (SOD/CAT mimetic, •OH scavenging) together with the pharmacological properties of EGCG. Notably, in this nanoplatform, PB NPs and EGCG demonstrate excellent synergistic therapeutic effects, characterized by enhanced ROS-responsive drug release and injured cardiac tissue-selected delivery. In vitro and in vivo studies confirmed the efficacy of PPFE NPs in neutralizing ROS, restoring mitochondrial homeostasis, and inhibiting apoptosis following I/R injury. Mechanistically, cardioprotection was mediated through the regulation of DJ-1 (PARK7) and its downstream pathways—Nrf2/ARE antioxidant signaling and ASK1/p38/JNK apoptotic regulation. Importantly, this study is the first to utilize native PB NPs as an EGCG carrier, exploiting their ROS scavenging ability and boronate ester bonds to improve EGCG loading efficiency and targeted delivery. Furthermore, we innovatively found that the combination of EGCG and DJ-1 may represent a key mechanism underlying the protective effects of EGCG against myocardial ischemia/reperfusion injury (MIRI). This work pioneers a ROS-responsive Prussian blue (PB) nanoplatform with superior synergistic efficacy. The study establishes PPFE NPs as a biocompatible nano-platform for myocardial I/R injury and provides a translatable strategy to optimize the clinical application of EGCG.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
·
2021
·Vol. 37
·期 9
·1271-1288
·
IF 5.203
Li Hao,Wu Shihao,Ma Xia,Li Xiao,Cheng Tianlin,Chen Zhifang,Wu Jing,Lv Longbao,Li Ling,Xu Liqi,Wang Wenchao,Hu Yingzhou,Jiang Haisong,Yin Yong,Qiu Zilong,Hu Xintian
Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.
研究领域:
神经科学
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分子生物学
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遗传学
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衰老研究
·
疾病模型
✓ 已验证
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2013
·Vol. 38
·期 9
·1871-1879
·
IF 2.125
Ruan Lin,Huang Huan-Sen,Jin Wen-Xiang,Chen Hai-Ming,Li Xiong-Juan,Gong Qing-Juan
Ischemic stroke is the most common type of stroke and brings about a big disease burden because of high mortality and disability in China. Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to possess anti-inflammatory and free radical scavenging effects and even regulate astrocyte activation, but the possible role of tetrandrine in ameliorating cerebral ischemia/reperfusion injury of ischemic stroke remains unknown. The aim of this study was to determine the effects of tetrandrine on neurological injury and differential proteomic changes induced by transient reversible middle cerebral artery occlusion (MCAO) in mice. Male Balb/c mice were divided into sham (n = 30), MCAO + saline as control (n = 30), and MCAO + Tet as tetrandrine-treated (n = 30) groups. Mice in the control and tetrandrine-treated groups underwent 120 min of MCAO following reperfusion. Immediately and 2 h after MCAO, the mice received either normal saline (sham operated and control groups) or tetrandrine (tetrandrine-treated group) intraperitoneally. Neurological defects, brain water content, and infarct volume at 24 h after stoke were used to evaluate neurological injury extent. Treatment with tetrandrine not only mitigated cerebral neurological deficits ( P < 0.05) and infarct size ( P < 0.01), but also decreased brian edema in the ischemic brain ( P < 0.05). Then, fluorescence two-dimensional difference in gel electrophoresis was used to detect our systematic differential profiling of proteomic changes responding to tetrandrine administration. We validated that the expression of GRP78, DJ-1 and HYOU1 was associated with neuroprotective effect of tetrandrine in MCAO model by Western blotting. These findings indicate a potential neuroprotective role of tetrandrine for ischemic stroke and yield insights into cellular and molecular mechanisms of tetrandrine taking place in ischemic stroke.
研究领域:
药理学
·
神经科学
·
蛋白质组学
✓ 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）