ONCOGENE
·
2018
·Vol. 37
·期 22
·2953-2966
·
IF 6.854
Cheng Yan,Gao Xing-Hua,Li Xian-Jing,Cao Qiu-Hua,Zhao Dan-Dan,Zhou Jin-Rong,Wu Hong-Xi,Wang Yun,You Lin-Jun,Yang Hong-Bao,He Yun-Long,Li Yong-Ren,Bian Jin-Song,Zhu Qing-Yi,Birnbaumer Lutz,Yang Yong
Depression drives cancer progression and induces poor clinical outcome. However, the mechanisms underlying depression and cancer outcomes are unclear. In this work, we investigated 98 prostate cancer patients and found that patients with high score of psychological depression were correlated with tumor invasion and metastasis. We found focal adhesion kinase (FAK) was increased in cancer patients with metastatic features and high score of depression. FAK knockdown completely blocked depression-promoted tumor invasion in orthotopic transplantation tumors. In Hi-myc mice and a murine model of depression, sympathetic activation was detected in the prostate tissue. Further we showed that FAK activation was dependent on a cAMP-PKA signaling pathway. Our results demonstrated that the activation of a sympathetic-FAK signaling pathway in prostate cancer patients with high degrees of depression facilitates tumor invasion. We suggest that blocking β2AR with propranolol or inhibiting FAK activation with PF562 271 may be novel strategies for depressed patients with invasive prostate cancer.
研究领域:
肿瘤学
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精神病学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR CELL
·
2024
·
IF 14.5
Wei Luo,Yunyuan Xu,Jie Cao,Xiaoyu Guo,Jingdan Han,Yuanyuan Zhang,Yuda Niu,Meiling Zhang,Yi Wang,Guohua Liang,Qian Qian,Song Ge,Kang Chong
While it is known that temperature sensors trigger calcium (Ca 2+ ) signaling to confer cold tolerance in cells, less is known about sensors that couple with other secondary messengers. Here, we identify a cold sensor complex of CHILLING-TOLERANCE DIVERGENCE 6 (COLD6) and osmotin-like 1 (OSM1), which triggers 2′,3′-cyclic adenosine monophosphate (2′,3′-cAMP) production to enhance cold tolerance in rice. COLD6, which is encoded by a major quantitative trait locus (QTL) gene, interacts with the rice G protein α subunit (RGA1) at the plasma membrane under normal conditions. Upon exposure to chilling, cold-induced OSM1 binds to COLD6, kicking out RGA1 from interaction. This triggers an elevation of 2′,3′-cAMP levels for enhancing chilling tolerance. Genetic data show that COLD6 negatively regulates cold tolerance and functionally depends on OSM1 in chilling stress. COLD6 alleles were selected during rice domestication. Knockout and natural variation of COLD6 in hybrid rice enhanced chilling tolerance, hinting design potential for breeding. This highlighted a module triggering 2′,3′-cAMP to improve chilling tolerance in crops.
研究领域:
植物学
·
遗传学
·
分子生物学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2025
·Vol. 82
·期 1
·1-16
·
IF 6.2
Zhao Xueqin,Li Yuanhao,Yang Liu,Chen Xi,Zhang Jialong,Chen Tong,Wang Haoqi,Li Fei,Cheng Chen,Wu Jingjing,Cong Jingjing,Yin Wenwei,Li Jing,Wang Xuefu
Acetaminophen (APAP) overdose induces acute liver injury and represents the most frequent cause of drug-induced liver injury worldwide. Macrophage-mediated inflammation plays detrimental roles during the early stage of liver injury. However, the potential targets regulating inflammation to improve drug-induced liver injury remains undefined. In this study, we reported that G protein-coupled receptor 35 (GPR35) improves drug-induced liver injury by blocking macrophage-mediated inflammation via the Gαs-cyclic AMP-protein kinase A (Gαs-cAMP-PKA) pathway. The ablation of GPR35 exacerbates APAP-induced liver injury, characterized by higher levels of alanine aminotransferase and aspartate aminotransferase in sera, larger damaged areas, and increased levels of pro-inflammatory cytokines. More hepatic macrophages appeared in the inflamed liver of mice with GPR35 deficiency. In contrast, the agonists of GPR35 alleviated APAP-induced liver injury. The depletion of macrophages abolished GPR35-mediated protection. Mechanistically, GPR35 ablation facilitated the activation of pro-inflammatory AKT, MAPK, and NF-κB signaling pathways at the downstream of Toll-like receptors in macrophages. GPR35 agonists activated Gαs-cAMP-PKA signaling to inhibit the activation of these pro-inflammatory signaling pathways and then suppress the inflammatory response in macrophages. Thus, our findings demonstrate that GPR35 prevents drug-induced liver injury by blocking macrophage-mediated inflammation via the Gαs-cAMP-PKA pathway, indicating that GPR35 is a potential target for the development of novel medicines that control drug-induced liver injury.
研究领域:
药理学
·
肝脏病学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Zhengyi Yang,Huixin Chen,Guo-Hua Zhong,Jie Liu
Soil microorganisms utilize extracellular DNA (eDNA)-based biofilms as a defense against xenobiotics. However, the specific effects and transfer pathways of eDNA under persistent agrochemical exposure remain unclear. This study examined the transfer dynamics of carbofuran-hydrolase gene pchA from Pseudomonas stutzeri PS21. During biofilm formation, pchA was released from eDNA, leading to an enrichment of beneficial microorganisms such as Acidobacteria and Elusimicrobia, which enhanced organic compound metabolism and improved soil microbiome resilience. An increase in the pchA-associated mobile genetic elements and the colocalization of pchA with other bacterial species indicated the potential horizontal gene transfer (HGT) under carbofuran exposure. Additionally, carbofuran triggered a cAMP-dependent apoptotic pathway, leading to a 59.6% increase in pchA copy number, which suggested that cAMP played a role in initiating HGT. In conclusion, the cAMP-mediated interspecific transfer of pchA could enhance microbial coadaptation to carbofuran contamination, thereby strengthening the collective defense of soil microbiome against agrochemical stress.
研究领域:
微生物学
·
环境科学
·
分子生物学
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DOI
PubMed
高影响因子
FUNGAL GENETICS AND BIOLOGY
·
2013
·
IF 3.263
Yibo Hu,Guodong Liu,Zhonghai Li,Yuqi Qin,Yinbo Qu,Xin Song
Heterotrimeric G proteins (G proteins) have been extensively investigated for their regulatory functions in morphogenesis and development in filamentous fungi. In addition, G proteins were also shown to be involved in the regulation of cellulase expression in some fungi. Here, we report the different regulatory effects of PGA3, a group III G protein α subunit, on the expressions of amylases and cellulases in Penicillium decumbens . Deletion of pga3 resulted in impaired amylase production and significantly decreased transcription of the major amylase gene amy15A . Supplementation of exogenous cAMP or its analog dibutyryl-cAMP restored amylase production in Δ pga3 strain, suggesting an essential role of PGA3 in amylase synthesis via controlling cAMP level. On the other hand, the transcription of major cellulase gene cel7A-2 increased, nevertheless cellulase activity in the medium was not affected, in Δ pga3 . The above regulatory effects of PGA3 are carbon source-independent, and are achieved, at least, by cAMP-mediated regulation of the expression level of transcription factor AmyR. The functions of PGA3 revealed by gene deletion were partially supported by the analysis of the mutant carrying dominantly-activated PGA3. The results provided new insights into the understanding of the physiological functions of G protein-cAMP pathway in filamentous fungi.
研究领域:
分子生物学
·
微生物学
·
真菌遗传学
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DOI
PubMed
高影响因子
Annals of Translational Medicine
·
2020
·
IF 3.297
Ying Li,Mingzhu Shan,Shihui Li,Yuechen Wang,Huan Yang,Ying Chen,Bing Gu,Zuobin Zhu
Background Candidiasis has long been a threat to human health, but cytotoxicity and resistance always block the usefulness of antifungal agents. The ability to switch between yeast and hypha is one of the most discussed virulence trait attributes of the human pathogenic fungus Candida albicans . The morphological transition provides a novel target for developing antifungal drugs. The aim of the present study was to explore the activity and mechanism of teasaponin (TS), a generally regarded as safe natural product, in inhibiting filamentation of C. albicans , hoping to provide an experimental basis for its clinical application. Methods The effect of TS on filamentation and biofilm formation of C. albicans was evaluated by XTT reduction assay and microscopy. The level of intracellular cAMP was measured to further explore the underlying mechanism. In addition, cytotoxicity of TS was evaluated by using MTT assay in vitro and Caenorhabditis elegans model in vivo . The potential of TS-resistance induction was tested by a serial passage experiment. Results TS displayed a moderate antifungal activity against the wild type, efflux pump mutant and multi-resistance C. albicans strains, and could effectively retard filamentation and biofilm formation with a low MIC value. Further mechanism investigation revealed that the reduced cAMP level inhibited filamentation and biofilm formation. In addition, TS showed no significant cytotoxicity in vitro or in vivo , and had little potential to develop resistance during long-time induction. Conclusions Our work evaluated the antifungal activity of TS against filamentation and biofilms formation of C. albicans and disclosed the underlying mechanism, which might provide useful clues for the potential clinical application of TS in fighting clinical fungal infections by targeting the virulence factors.
研究领域:
微生物学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2014
·
IF 3.259
Jianxia Sun,Shun Bai,Weibin Bai,Feiyan Zou,Lei Zhang,Guoqiang Li,Yunfeng Hu,Mingwei Li,Rian Yan,Zhijian Su,Yadong Huang
1,3-Dichloro-2-propanol (1,3-DCP) is a well-known food processing contaminant that has been shown to impede male reproductive function. However, its mechanism of action remains elusive. In this study, the effects of 1,3-DCP on progesterone production were investigated using the R2C Leydig cell model. 1,3-DCP significantly reduced cell viability from 7.48% to 97.4% at doses comprised between 0.5 and 6 mM. Single cell gel/comet assays and atomic force microscopy assays showed that 1,3-DCP induced early phase cell apoptosis. In addition, 1,3-DCP significantly reduced progesterone production detected by radioimmunoassay (RIA). The results from quantitative polymerase chain reaction and western blotting demonstrated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase were significantly down-regulated in R2C cells. Particularly, the change rhythm of Star expression was highly consistent with progesterone production. Furthermore, the cyclic adenosine monophosphate (cAMP) and the mitochondrial membrane potential mediated by ROS, which are involved in regulating progesterone synthesis were also decreased in response to the 1,3-DCP treatment. Overall, the data presented here suggested that 1,3-DCP interferes with the male steroidogenic capacity mainly by down-regulating the level of cAMP and the key enzymes involved in the androgen synthesis pathway.
研究领域:
生殖生物学
·
毒理学
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2021
·
IF 3.757
Yonghua Hu,Yuan Zhou,Xiaohua Hu,Qiaoling Chen,Yan Shi,Jiangxing Zhuang,Qin Wang
Cefotaxime sodium (CTX) was found to inhibit the activity of mushroom tyrosinase. The present study was conducted to investigate its inhibition of melanogenesis in B16F10 cells. CTX was found to inhibit melanin synthesis in B16F10 cells at a concentrations less than 200 μmol/L with no cytotoxicity. CTX reduced tyrosinase activity in a dose-dependent manner. CTX inhibited melanin formation from the results of the Masson-Fontana melanin staining and transmission electron microscope CTX influenced melanin production by influencing the expression of the proteins MITF, TRP-1, TRP-2 and TYR. Furthermore, CTX could down-regulate the intracellular cAMP/PKA/CREB contents, affecting the expression of MITF, and further down-regulate the expression of TRP-1, TRP-2 and TYR to inhibit melanin. Furthermore, CTX has been shown to inhibit body pigmentation in zebrafish. These results may provide a theoretical foundation for the new application of CTX in the field of medicine.
研究领域:
药理学
·
细胞生物学
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分子生物学
✓ 已验证
DOI
高影响因子
mBio
·
2025
·
IF 4.7
Kaili Duan,Shaozhe Qin,Fangling Cui,Liangyuan Zhao,Yongqing Huang,Jin-Rong Xu,Guanghui Wang
Deoxynivalenol (DON), a mycotoxin primarily produced by Fusarium species, is commonly found in cereal grains and poses risks to human and animal health, as well as global grain trade. This study demonstrates that methyl jasmonate (MeJA), a natural plant hormone, inhibits the growth and conidiation of Fusarium graminearum. Importantly, MeJA significantly reduces DON production by suppressing TRI gene expression and toxisome formation. To explore the molecular mechanism, we identified MeJA-tolerant mutants, including a transcription factor MRT1 and cAMP-PKA pathway-related genes (FgGPA1 and FgSNT1). MeJA treatment reduced PKA activity and intracellular cAMP levels in F. graminearum, suggesting it targets the cAMP-PKA pathway. Notably, the MeJA-resistant mutant FgGPA1R178H enhanced fungal growth, DON production, and cAMP levels in the presence of MeJA. Exogenous cAMP alleviated MeJA’s inhibitory effects on DON production, further supporting this pathway’s involvement. Interestingly, MeJA had no effect on all three MAP kinase pathways (Mgv1, Gpmk1, and FgHog1). Truncated and phospho-mimicking mutations in Mrt1 or FgSnt1 conferred MeJA resistance, suggesting they may act downstream of the cAMP-PKA pathway. In conclusion, MeJA presents a promising approach to control F. graminearum growth and DON production.
研究领域:
植物病理学
·
分子生物学
·
真菌学
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产品关联
DOI
PubMed
高影响因子
EMBO JOURNAL
·
2024
·
IF 9.4
GengShan,YangShan,TangXuejiao,XueShiyao,LiKe,LiuDongfang,ChenChen,ZhuZhiming,ZhengHongting,WangYuanqiang,YangGangyi,LiLing,YangMengliu
Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut – brain – liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion in the intestinal epithelium, thus inhibiting hepatic glucose production. The intestinal nesfatin-1 -MC4R-cAMP-GLP-1 pathway and systemic gut-brain communication are required for nesfatin-1 - mediated regulation of liver energy metabolism. These findings reveal a novel mechanism of hepatic glucose production control by gut hormones through the central nervous system.
研究领域:
内分泌学
·
代谢学
·
胃肠病学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
Science Translational Medicine
·
2024
·Vol. 16
·期 775
·
IF 15.8
Xingyuan Jiao,Yihu Li,Zhihang Chen,Qi Zhang,Rui He,Yinbing Huang,Zhixiang Zuo
In liver transplantation, donor livers are typically stored in a preservation solution at 4°C for up to 12 hours. However, this short preservation duration can lead to various issues, such as suboptimal donor-recipient matching and limited opportunities for organ sharing. Previous studies have developed a long-term preservation method called supercooling liver preservation (SLP) to address these issues. However, in this study using a rat model, we observed that long-term SLP led to more severe liver damage compared with clinically prevalent traditional static cold storage (SCS) for durations less than 8 hours. To understand the potential mechanism of SLP-induced liver injury, we conducted an integrative metabolomic, transcriptomic, and proteomic analysis. We identified the PDE3B-cAMP-autophagy pathway as a key determinant of SLP-induced liver injury. Specifically, we found that PDE3B was elevated during SLP, which promoted a reduction of cAMP metabolites, triggering an AMPK-dependent autophagy process that led to liver injury in rats. We found that blocking the reduction in cAMP using the PDE3B inhibitor cilostamide inhibited autophagy and substantially ameliorated liver injury during 48-hour SLP in rat livers. Furthermore, we validated the effectiveness of cilostamide treatment in preventing liver injury in pig and human liver 48-hour SLP models. In summary, our results reveal that metabolic reprogramming involving the PDE3B-cAMP-autophagy axis is the key determinant of liver injury in long-term SLP and provide an early therapeutic strategy to prevent liver injury in this setting.
研究领域:
器官移植
·
肝病学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD MICROBIOLOGY
·
2025
·
IF 4.6
Xiaoyun Zhang,Yu Zhao,Esa Abiso Godana,Jun Li,Solairaj Dhanasekarana,Yuanyuan Xie,Lina Zhao,Hongyin Zhang
Sour rot caused by Aspergillus carbonarius is a common postharvest disease of grapes, which leads to the declined fruit quality and serious economic losses of grape industry. In this study, we investigated the control effectiveness of Sporidiobolus pararoseus Y16 induced by cyclic adenosine monophosphate (cAMP) against postharvest sour rot of grapes, and explored the potential action mechanisms. The outcomes presented that S. pararoseus Y16 induced by 0.05 mM cAMP for 24 h further mitigated sour rot compared with S. pararoseus Y16 cultured without cAMP. cAMP could enhance the colonization ability of S. pararoseus Y16. More importantly, cAMP-induced yeast further boosted the activities of antioxidant enzymes and the expression level of the corresponding genes, thus improving the ability of scavenging reactive oxygen species of grapes. Moreover, S. pararoseus Y16 induced by cAMP further mounted the activities of defensive enzymes in grapes, as well as the expression level of the corresponding genes, thereby strengthening the disease resistance of grapes. Additionally, the accumulation of resistant secondary metabolites was further augmented, which also contributed to improving the disease resistance of grapes. This research revealed that cAMP-induced culture is helpful to improve the effectiveness of S. pararoseus Y16 in controlling postharvest sour rot of grapes. This research provides a novel and effective biocontrol strategy for the grape industry to mitigate postharvest sour rot. By using cAMP-induced antagonistic microorganisms, the reliance on chemical fungicides could be potentially reduced, thereby promoting sustainable agricultural practices and enhancing the overall quality and safety of grape products.
研究领域:
植物病理学
·
微生物学
·
采后技术
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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）