Category: 347174-05-4

Xie, Zhenxing; Xu, Mang; Xie, Jie; Liu, Tao; Xu, Xie; Gao, Wei; Li, Zhanfei; Bai, Xiangjun; Liu, Xinghua published the artcile< Inhibition of ferroptosis attenuates glutamate excitotoxicity and nuclear autophagy in a CLP septic mouse model>, Computed Properties of 347174-05-4, the main research area is ferroptosis glutamate excitotoxicity nuclear autophagy sepsis associated encaphalopathy.

Sepsis-associated encephalopathy (SAE) often manifests in severe diffuse cerebral dysfunction due to an aberrant systemic immune response to infection. The underlying pathophysiol. of SAE is not entirely understood but is likely a multifactorial process that involves disruption in cell death mechanism. Ferroptosis is a novel formof programmed cell death characterized by iron accumulation and lipid peroxidation, leading to inflammatory cascade and glutamate release. We hypothesized that ferroptosis is involved in the glutamate-mediated excitotoxic neuron injury during the uncontrolled neural inflammatory process of SAE. Inhibiting ferroptosis with ferrostatin-1 (Fer-1) could alleviate glutamate excitotoxicity and reduce neuron death of SAE, potentially improving prognosis. We found that in the cecal ligation and puncture (CLP) sepsis model, ferroptosis occurred increasingly in the cerebrum, characterized by glutathione-dependent antioxidant enzyme glutathione peroxidase 4 (GPX4) inactivation, transferrin upregulation, mitochondria shrink and malondialdehyde (MDA) increased. Fer-1 treatment downregulated cerebral ferroptosis and alleviated glutamate excitotoxicity via dampening system xc-(SXC) and glutamate receptor N-methyl-D-asperate receptor subunit 2. Combined with an observed reduction in calcium transporter PLCG and PLCB activation, these processes ultimately protected the integrities of synapses and neurons during SAE. Fer-1 treatment also rescued sepsis-induced nuclear autophagy and improved the behaviors of tail suspension test and novel object recognition test in septic mice. Conclusively, our results suggested that inhibition of ferroptosis could attenuate glutamate excitotoxicity and SAE outcomes.

Shock published new progress about AMPA receptors, GluR1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Computed Properties of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wang, Xiaoyu; Wan, Meiyin; Zhang, Lei; Dai, Yongdong; Hai, Yang; Yue, Chenda; Xu, Junqi; Ding, Yadan; Wang, Mei; Xie, Jianping; Lei, Xia; Zhong, Julia-Li published the artcile< ALA_PDT Promotes Ferroptosis-Like Death of Mycobacterium abscessus and Antibiotic Sterilization via Oxidative Stress>, Category: esters-buliding-blocks, the main research area is Mycobacterium abscessus 5aminolevulinic acid photodynamic therapy oxidative tress; ferroptosis antibiotic; ALA_PDT; Mycobacterium abscessus; antibiotic resistance; ferroptosis; heme oxygenase MAB_4773.

Mycobacterium abscessus is one of the common clin. non-tuberculous mycobacteria (NTM) that can cause severe skin infection. 5-Aminolevulinic acid photodynamic therapy (ALA_PDT) is an emerging effective antimicrobial treatment. To explore whether ALA_PDT can be used to treat M. abscessus infections, we conducted a series of experiments in vitro. We found that ALA_PDT can kill M. abscesses. Mechanistically, we found that ALA_PDT promoted ferroptosis-like death of M. abscesses, and the ROS scavenger N-Acetyl-L-cysteine (NAC) and ferroptosis inhibitor Ferrostatin-1 (Fer-1) can mitigate the ALA_PDT-mediated sterilization. Furthermore, ALA_PDT significantly up-regulated the transcription of heme oxygenase MAB_4773, increased the intracellular Fe2+ concentration and altered the transcription of M. abscessus iron metabolism genes. ALA_PDT disrupted the integrity of the cell membrane and enhanced the permeability of the cell membrane, as evidenced by the boosted sterilization effect of antibiotics. In summary, ALA_PDT can kill M. abscesses via promoting the ferroptosis-like death and antibiotic sterilization through oxidative stress by changing iron metabolism The study provided new mechanistic insights into the clin. efficacy of ALA_PDT against M. abscessus.

Antioxidants published new progress about Antibiotics. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Category: esters-buliding-blocks.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wang, Shaohui; Jiang, Yao; Liu, Yabo; Liu, Qianhui; Sun, Hongwei; Mei, Mengjie; Liao, Xiaomei published the artcile< Ferroptosis promotes microtubule-associated protein tau aggregation via GSK-3β activation and proteasome inhibition>, Product Details of C15H22N2O2, the main research area is neuroblastoma cell ferroptosis microtubule tau aggregation GSK3b proteasome; Ferroptosis; Glycogen synthase kinase-3β; Tau; Ubiquitin proteasome system.

Ferroptosis is a form of regulated cell death resulting from iron accumulation and lipid peroxidation Iron dyshomeostasis and peroxidation damage of neurons in some particular brain regions are closely related to a wide range of neurodegenerative diseases known as “”tauopathies,”” in which intracellular aggregation of microtubule-associated protein tau is the common neuropathol. feature. However, the relationship between ferroptosis and tau aggregation is not well understood. The current study demonstrates that erastin-induced ferroptosis can promote tau hyperphosphorylation and aggregation in mouse neuroblastoma cells (N2a cells). Moreover, ferroptosis inhibitor ferrostatin-1 can alleviate tau aggregation effectively. In-depth mechanism research indicates that activated glycogen synthase kinase-3β (GSK-3β) is responsible for the abnormal hyperphosphorylation of tau. More importantly, proteasome inhibition can exacerbate tau degradation obstacle and accelerate tau aggregation in the process of ferroptosis. Our results indicate that ferroptosis can lead to abnormal aggregation of tau protein and might be a promising therapeutic target of tauopathies.

Molecular Neurobiology published new progress about Autophagy. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Product Details of C15H22N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Menon, Archita Venugopal; Liu, Jing; Tsai, Hanting Phoebe; Zeng, Lingxue; Yang, Seungjeong; Asnani, Aarti; Kim, Jonghan published the artcile< Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease>, Name: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is heme oxygenase cardiac ferroptosis sickle cell disease.

Sickle cell disease (SCD) is characterized by increased hemolysis, which results in plasma heme overload and ultimately cardiovascular complications. Here, we hypothesized that increased heme in SCD causes upregulation of heme oxygenase 1 (Hmox1), which consequently drives cardiomyopathy through ferroptosis, an iron-dependent non-apoptotic form of cell death. First, we demonstrated that the Townes SCD mice had higher levels of hemopexin-free heme in the serum and increased cardiomyopathy, which was corrected by hemopexin supplementation. Cardiomyopathy in SCD mice was associated with upregulation of cardiac Hmox1, and inhibition or induction of Hmox1 improved or worsened cardiac damage, resp. Because free iron, a product of heme degradation through Hmox1, has been implicated in toxicities including ferroptosis, we evaluated the downstream effects of elevated heme in SCD. Consistent with Hmox1 upregulation and iron overload, levels of lipid peroxidation and ferroptotic markers increased in SCD mice, which were corrected by hemopexin administration. Moreover, ferroptosis inhibitors decreased cardiomyopathy, whereas a ferroptosis inducer erastin exacerbated cardiac damage in SCD and induced cardiac ferroptosis in nonsickling mice. Finally, inhibition or induction of Hmox1 decreased or increased cardiac ferroptosis in SCD mice, resp. Together, our results identify ferroptosis as a key mechanism of cardiomyopathy in SCD.

Blood published new progress about Blood serum. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Name: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Shimizu, Junji; Murao, Atsushi; Nofi, Colleen; Wang, Ping; Aziz, Monowar published the artcile< Extracellular CIRP promotes GPX4-mediated ferroptosis in sepsis>, Reference of 347174-05-4, the main research area is ferroptosis eCIRP therapeutic target inflammation sepsis; GPX4; acute lung injury; eCIRP; ferroptosis; lung; macrophage; sepsis.

Sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated mol. pattern (DAMP) that promotes inflammation and induces cell death via apoptosis, NETosis, and/or pyroptosis. Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxide on cellular membranes. We hypothesize that eCIRP induces ferroptosis in macrophages and lung tissue during sepsis. RAW 264.7 cells stimulated with recombinant murine (rm) CIRP significantly decreased the expression of glutathione peroxidase 4 (GPX4), a neg. regulator of ferroptosis, and increased lipid reactive oxygen species (ROS) in a TLR4 dependent manner. In TLR4-/- peritoneal macrophages, depression of GPX4 expression and increase in lipid ROS levels were attenuated after rmCIRP-treatment compared to WT macrophages. rmCIRP also induced cell death in RAW 264.7 cells which was corrected by the ferroptosis inhibitor, ferrostatin-1 (Fer-1). I.p. injection of rmCIRP decreased GPX4 expression and increased lipid ROS in lung tissue, whereas the increase of lipid ROS was reduced by Fer-1 treatment. GPX4 expression was significantly decreased, while malondialdehyde (MDA), iron levels, and injury scores were significantly increased in lungs of WT mice after cecal ligation and puncture (CLP)-induced sepsis compared to CIRP-/- mice. Treatment with C23, a specific eCIRP inhibitor, in CLP mice alleviated the decrease in GPX4 and increase in MDA levels of lung tissue. These findings suggest that eCIRP induces ferroptosis in septic lungs by decreasing GPX4 and increasing lipid ROS. Therefore, regulation of ferroptosis by targeting eCIRP may provide a new therapeutic approach in sepsis and other inflammatory diseases.

Frontiers in Immunology published new progress about Apoptosis. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Reference of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Yoshioka, Hiromasa; Kawamura, Tatsuro; Muroi, Makoto; Kondoh, Yasumitsu; Honda, Kaori; Kawatani, Makoto; Aono, Harumi; Waldmann, Herbert; Watanabe, Nobumoto; Osada, Hiroyuki published the artcile< Identification of a Small Molecule That Enhances Ferroptosis via Inhibition of Ferroptosis Suppressor Protein 1 (FSP1)>, Product Details of C15H22N2O2, the main research area is anticancer GPX4 FSP1 inhibitor NPD4928 synergistic effects ferroptosis enhancer.

Glutathione peroxidase 4 (GPX4) is an intracellular enzyme that oxidizes glutathione while reducing lipid peroxides, and is a promising target for cancer therapy. Till date, several GPX4 inhibitors have been reported to exhibit cytotoxicity against cancer cells. However, some cancer cells are less sensitive to the known GPX4 inhibitors. This study aimed to explore compounds showing synergistic effects with GPX4 inhibitors. We screened a chem. library and identified a compound named NPD4928 (I), whose cytotoxicity was enhanced in the presence of a GPX4 inhibitor. Furthermore, we identified ferroptosis suppressor protein 1 (FSP1) as its target protein. The results indicate that NPD4928 enhanced the sensitivity of various cancer cells to GPX4 inhibitors, suggesting the combination to possibly have therapeutic potential via the induction of ferroptosis.

ACS Chemical Biology published new progress about Antitumor agents. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Product Details of C15H22N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Gao, Meng; Hu, Jun; Zhu, Yuejie; Wang, Xianqing; Zeng, Shumin; Hong, Yijiang; Zhao, Guang published the artcile< Ferroptosis and Apoptosis Are Involved in the Formation of L-Selenomethionine-Induced Ocular Defects in Zebrafish Embryos>, Application of C15H22N2O2, the main research area is Zebrafish embryos ferroptosis apoptosis selenomethionine; L-selenomethionine; ROS; apoptosis; ferroptosis; microphthalmia.

Selenium is an essential trace element for humans and other vertebrates, playing an important role in antioxidant defense, neurobiol. and reproduction However, the toxicity of excessive selenium has not been thoroughly evaluated, especially for the visual system of vertebrates. In this study, fertilized zebrafish embryos were treated with 0.5μM L-selenomethionine to investigate how excessive selenium alters zebrafish eye development. Selenium-stressed zebrafish embryos showed microphthalmia and altered expression of genes required for retinal neurogenesis. Moreover, ectopic proliferation, disrupted mitochondrial morphol., elevated ROS-induced oxidative stress, apoptosis and ferroptosis were observed in selenium-stressed embryos. Two antioxidants-reduced glutathione (GSH) and N-acetylcysteine (NAC)-and the ferroptosis inhibitor ferrostatin (Fer-1) were unable to rescue selenium-induced eye defects, but the ferroptosis and apoptosis activator cisplatin (CDDP) was able to improve microphthalmia and the expression of retina-specific genes in selenium-stressed embryos. In summary, our results reveal that ferroptosis and apoptosis might play a key role in selenium-induced defects of embryonic eye development. The findings not only provide new insights into selenium-induced cellular damage and death, but also important implications for studying the association between excessive selenium and ocular diseases in the future.

International Journal of Molecular Sciences published new progress about Antioxidants. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Application of C15H22N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Hu, Jianqiang; Gu, Wenjing; Ma, Ning; Fan, Xiaoye; Ci, Xinxin published the artcile< Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signalling pathway>, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is leonurine cisplatin ferroptosis acute kidney injury Nrf signalling pathway; Nrf2; cisplatin-induced acute kidney injury; ferroptosis; leonurine.

Evidence indicates that ferroptosis plays a key role in acute kidney injury induced by cisplatin. The Nrf2/NRF2 pathway regulates oxidative stress, lipid peroxidation and pos. regulates cisplatin-induced acute kidney injury, but its effect along with the alkaloid leonurine, found in motherwort, on ferroptosis after such acute kidney injury remains unclear. The anti-ferroptotic effects of Nrf2 and leonurine were assessed in a mouse model of cisplatin-induced acute kidney injury. In vitro, the effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, aggravating cisplatin-induced acute kidney injury. Leonurine activated Nrf2 and prevented iron accumulation, lipid peroxidation and ferroptosis in vitro, being abolished in siNrf2-treated cells. Moreover, leonurine potently inhibited cisplatin-induced renal damage, as assessed by of serum creatinine, blood urea nitrogen, kidney injury mol.-1 and NGAL. Importantly, leonurine activated the Nrf2 antioxidative pathway and preventing changes in ferroptosis-related morphol. and biochem. indicators, malondialdehyde level, SOD and GSH depletion, and GPX4 and xCT down-regulation, in cisplatin-induced acute kidney injury. Nrf2 KO mice were more susceptible to ferroptosis after cisplatin-induced acute kidney injury than control mice. The protective effects of leonurine on acute kidney injury and ferroptosis were largely abolished in Nrf2 KO mice. These data suggest that renal protective effects of Nrf2 activation on cisplatin-induced acute kidney injury are achieved, at least partially, by inhibiting lipid peroxide-mediated ferroptosis, highlighting the potential of leonurine in acute kidney injury treatment.

British Journal of Pharmacology published new progress about Acute kidney injury. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Gao, Meng; Hu, Jun; Zhu, Yuejie; Wang, Xianqing; Zeng, Shumin; Hong, Yijiang; Zhao, Guang published the artcile< Ferroptosis and Apoptosis Are Involved in the Formation of L-Selenomethionine-Induced Ocular Defects in Zebrafish Embryos>, Application of C15H22N2O2, the main research area is Zebrafish embryos ferroptosis apoptosis selenomethionine; L-selenomethionine; ROS; apoptosis; ferroptosis; microphthalmia.

Selenium is an essential trace element for humans and other vertebrates, playing an important role in antioxidant defense, neurobiol. and reproduction However, the toxicity of excessive selenium has not been thoroughly evaluated, especially for the visual system of vertebrates. In this study, fertilized zebrafish embryos were treated with 0.5μM L-selenomethionine to investigate how excessive selenium alters zebrafish eye development. Selenium-stressed zebrafish embryos showed microphthalmia and altered expression of genes required for retinal neurogenesis. Moreover, ectopic proliferation, disrupted mitochondrial morphol., elevated ROS-induced oxidative stress, apoptosis and ferroptosis were observed in selenium-stressed embryos. Two antioxidants-reduced glutathione (GSH) and N-acetylcysteine (NAC)-and the ferroptosis inhibitor ferrostatin (Fer-1) were unable to rescue selenium-induced eye defects, but the ferroptosis and apoptosis activator cisplatin (CDDP) was able to improve microphthalmia and the expression of retina-specific genes in selenium-stressed embryos. In summary, our results reveal that ferroptosis and apoptosis might play a key role in selenium-induced defects of embryonic eye development. The findings not only provide new insights into selenium-induced cellular damage and death, but also important implications for studying the association between excessive selenium and ocular diseases in the future.

International Journal of Molecular Sciences published new progress about Antioxidants. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Application of C15H22N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Hu, Jianqiang; Gu, Wenjing; Ma, Ning; Fan, Xiaoye; Ci, Xinxin published the artcile< Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signalling pathway>, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is leonurine cisplatin ferroptosis acute kidney injury Nrf signalling pathway; Nrf2; cisplatin-induced acute kidney injury; ferroptosis; leonurine.

Evidence indicates that ferroptosis plays a key role in acute kidney injury induced by cisplatin. The Nrf2/NRF2 pathway regulates oxidative stress, lipid peroxidation and pos. regulates cisplatin-induced acute kidney injury, but its effect along with the alkaloid leonurine, found in motherwort, on ferroptosis after such acute kidney injury remains unclear. The anti-ferroptotic effects of Nrf2 and leonurine were assessed in a mouse model of cisplatin-induced acute kidney injury. In vitro, the effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, aggravating cisplatin-induced acute kidney injury. Leonurine activated Nrf2 and prevented iron accumulation, lipid peroxidation and ferroptosis in vitro, being abolished in siNrf2-treated cells. Moreover, leonurine potently inhibited cisplatin-induced renal damage, as assessed by of serum creatinine, blood urea nitrogen, kidney injury mol.-1 and NGAL. Importantly, leonurine activated the Nrf2 antioxidative pathway and preventing changes in ferroptosis-related morphol. and biochem. indicators, malondialdehyde level, SOD and GSH depletion, and GPX4 and xCT down-regulation, in cisplatin-induced acute kidney injury. Nrf2 KO mice were more susceptible to ferroptosis after cisplatin-induced acute kidney injury than control mice. The protective effects of leonurine on acute kidney injury and ferroptosis were largely abolished in Nrf2 KO mice. These data suggest that renal protective effects of Nrf2 activation on cisplatin-induced acute kidney injury are achieved, at least partially, by inhibiting lipid peroxide-mediated ferroptosis, highlighting the potential of leonurine in acute kidney injury treatment.

British Journal of Pharmacology published new progress about Acute kidney injury. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics