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Search results for: Caspase 12 Inhibitor Z ATAD FMK

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#35918751   2022/08/02 To Up

Toxoplasma gondii dense granule protein 3 promotes endoplasmic reticulum stress-induced apoptosis by activating the PERK pathway.

Toxoplasma gondii is a neurotropic single-celled parasite that can infect mammals, including humans. Central nervous system infection with T. gondii infection can lead to Toxoplasma encephalitis. Toxoplasma infection can cause endoplasmic reticulum (ER) stress and unfolded protein response (UPR) activation, which ultimately can lead to apoptosis of host cells. The dense granule protein GRA3 has been identified as one of the secretory proteins that contribute to the virulence of T. gondii; however, the mechanism remains enigmatic.
Cudjoe Obed, Minmin Wu, Ying Chen, Ran An, Haijian Cai, Qingli Luo, Li Yu, Jie Wang, Fang Liu, Jilong Shen, Jian Du

2683 related Products with: Toxoplasma gondii dense granule protein 3 promotes endoplasmic reticulum stress-induced apoptosis by activating the PERK pathway.

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#33133437   2020/10/25 To Up

Memantine, Simvastatin, and Epicatechin Inhibit 7-Ketocholesterol-induced Apoptosis in Retinal Pigment Epithelial Cells But Not Neurosensory Retinal Cells In Vitro.

7-ketocholesterol (7kCh), a natural byproduct of oxidation in lipoprotein deposits is implicated in the pathogenesis of diabetic retinopathy and age-related macular degeneration (AMD). This study was performed to investigate whether several clinical drugs can inhibit 7kCh-induced caspase activation and mitigate its apoptotic effects on retinal cells in vitro.
Aneesh Neekhra, Julia Tran, Parsa R Esfahani, Kevin Schneider, Khoa Pham, Ashish Sharma, Marilyn Chwa, Saurabh Luthra, Ana L Gramajo, Saffar Mansoor, Baruch D Kuppermann, M Cristina Kenney

1323 related Products with: Memantine, Simvastatin, and Epicatechin Inhibit 7-Ketocholesterol-induced Apoptosis in Retinal Pigment Epithelial Cells But Not Neurosensory Retinal Cells In Vitro.

1x10e7 cells96 assays1 mg2 ml1 mg1x10e7 cells-10 ug1x10e7 cells

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#30605698   2018/12/31 To Up

Alpha-lipoic acid protects against cadmium-induced neuronal injury by inhibiting the endoplasmic reticulum stress eIF2α-ATF4 pathway in rat cortical neurons in vitro and in vivo.

The heavy metal cadmium (Cd) is well known to be neurotoxic. Studies have shown that apoptosis plays an essential role in Cd-induced brain injury; however, the mechanisms underlying this injury accompanied by apoptosis have yet to be elucidated. The endoplasmic reticulum (ER) stress plays a key part in the regulation of apoptosis. ER stress is defined as accumulation of unfolded or misfolded proteins in the ER. Here, we demonstrated the role of ER stress on Cd-evoked apoptosis in neuronal cells, as well as the neuroprotective effects of the antioxidant alpha-lipoic acid (α-LA) on Cd-induced ER stress and neuronal injury. In vitro, we observed that Cd activated ER associated proteins via the eIF2α-ATF4 pathway in primary rat cerebral cortical neurons. Furthermore, the ER-stress inhibitor salubrinal blocked the dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and significantly reduced the induction of ER stress marker CHOP, the increase of the B-cell lymphoma-2 associate X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, and apoptosis induced by Cd. In addition, Z-ATAD-FMK (a caspase-12 inhibitor) counteracted the Cd-induced activation of caspase-12 and -3, and apoptosis. These in vitro results collectively suggested that ER stress was required for Cd-induced neuronal apoptosis. Importantly, α-LA inhibited the activation of the ER stress eIF2α-ATF4 pathway, the increase of the Bax/Bcl-2 ratio, the activation of caspase-12 and -3, and the apoptosis induced by Cd. In vivo, we also found that the administration of α-LA alleviated Cd-induced neuronal injury, inhibited the activation of the ER stress eIF2α-ATF4 pathway, restored the Bax/Bcl-2 ratio, and prevented the activation of caspase-12 and -3. Taken together, our results demonstrated that Cd triggered protein changes in the ER accompanied by apoptosis via the eIF2α-ATF4 signaling pathway in the neuronal cells of rats, both in vitro and in vivo. Furthermore, we demonstrated for the first time that α-LA protected neurons from Cd-induced injury partly by inhibiting ER stress in rat cerebral cortical neurons.
Yan Yuan, Jinlong Yang, Jie Chen, Shiwen Zhao, Tao Wang, Hui Zou, Yi Wang, Jianhong Gu, Xuezhong Liu, Jianchun Bian, Zongping Liu

2208 related Products with: Alpha-lipoic acid protects against cadmium-induced neuronal injury by inhibiting the endoplasmic reticulum stress eIF2α-ATF4 pathway in rat cortical neurons in vitro and in vivo.

100 UG10 2 Pieces/Box100ug Lyophilized100.00 ug100ug Lyophilized100ug2 Pieces/Box100ug10mg1 ml

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#28825094   // To Up

Activation of caspase-12 at early stage contributes to cardiomyocyte apoptosis in trauma-induced secondary cardiac injury.

Trauma-induced secondary cardiac injury (TISCI) is associated with increased adverse cardiac events and death. We have previously reported that TISCI results in myocardial apoptosis and secondary cardiac dysfunction. However, the underlying mechanism is unclear. To identify the time course of trauma-induced cardiomyocyte apoptosis and possible apoptotic pathway, traumatic rat models were built with Noble-Collip drum. Meanwhile, normal rat cardiomyocytes were cultured with traumatic plasma (TP) for 48 h. Cardiomyocyte apoptosis, cardiac function and the apoptosis related enzymes, including caspase-3, -8, -9, and -12, were determined. The results showed that there was no direct injury of rat hearts immediately after trauma. However, compared with hearts from the sham rats, hearts isolated from traumatic rats exhibited reduced +dP/dT and -dP/dT 24 h after trauma. In traumatic rats, myocardial apoptotic index and caspase-3 activity obviously increased 6 h after trauma, and achieved the maximal value 12 h after trauma. The activity and expression of caspase-12, an endoplasmic reticulum (ER) stress-specific caspase, elevated markedly 3 h after trauma and reached its peak 6 h after trauma. Otherwise, caspase-8 (extrinsic apoptotic pathway) and caspase-9 (intrinsic apoptotic pathway) in the myocardial tissue of traumatic rats were activated 24 h after trauma. Meanwhile, incubation of normal rat cardiomyocytes with TP increased caspase-12 activity at 6 h, caspase-3 activity at 12 h, caspase-8 and -9 activities at 24 h, respectively. TP-induced cardiomyocyte apoptosis was virtually abolished by Z-ATAD-FMK (a caspase-12 specific inhibitor). In addition, there was a significant negative correlation between myocardial caspase-12 activity and trauma-induced secondary cardiac dysfunction. Our present study demonstrated that caspase-12 is firstly activated and plays an important role in TISCI rats. Inhibition of caspase-12 mediated apoptosis may be a novel strategy in ameliorating posttraumatic cardiomyocyte apoptosis and secondary cardiac injury.
Zi Yan, Jin-Ling He, Li Guo, Hui-Jun Zhang, Su-Li Zhang, Jie Zhang, Yong-Jin Wen, Cheng-Zhang Cao, Jie Wang, Jin Wang, Ming-Sheng Zhang, Feng Liang

1663 related Products with: Activation of caspase-12 at early stage contributes to cardiomyocyte apoptosis in trauma-induced secondary cardiac injury.

20 100 µl (2 mM)20 µl (10 mM)100 100ug100 20 100ug3 mg8 x 25 ul

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#26489755   2015/10/21 To Up

T. gondii rhoptry protein ROP18 induces apoptosis of neural cells via endoplasmic reticulum stress pathway.

The neurotropic parasite T. gondii is widespread among mammalian hosts including humans. During the course of T. gondii infection, the central nervous system is the most commonly damaged of all invasive organs. The polymorphic rhoptry protein ROP18 has been identified as a key factor in the pathogenesis of T. gondii; however, the molecular mechanism by which this protein exerts neuropathogenesis remains elusive.
Lijuan Wan, Lingli Gong, Wei Wang, Ran An, Meijuan Zheng, Zongru Jiang, Yuewen Tang, Yihua Zhang, He Chen, Li Yu, Jilong Shen, Jian Du

1979 related Products with: T. gondii rhoptry protein ROP18 induces apoptosis of neural cells via endoplasmic reticulum stress pathway.

100ul5001005 x 10A5 cells/vial100 ug1001010100 ug/vial100ug/vial1.5 x 10^6 cells

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#26361144   2015/09/08 To Up

Endoplasmic reticulum stress activation mediates Ginseng Rg3-induced anti-gallbladder cancer cell activity.

In the current study, we examined the potential effect of Ginsenoside Rg3 against gallbladder cancer cells, the underlying signaling mechanisms were also studied. We demonstrated that Rg3 exerted potent cytotoxic and pro-apoptotic activity against established and primary human gallbladder cancer cells. Yet it was safe to non-cancerous gallbladder epithelial cells. At the molecular level, we showed that Rg3 induced endoplasmic reticulum (ER) stress activation, the latter was evidenced by C/EBP homologous protein (CHOP) upregulation, inositol-requiring enzyme 1 (IRE1)/PKR-like endoplasmic reticulum kinase (PERK) phosphorylations, and caspase-12 activation in gallbladder cancer cells. Reversely, the ER stress inhibitor salubrinal, the caspase-12 inhibitor z-ATAD-fmk as well as CHOP shRNA knockdown significantly attenuated Rg3-induced cytotoxicity against gallbladder cancer cells. In vivo, we showed that Rg3 oral administration significantly inhibited GBC-SD gallbladder cancer xenograft growth in nude mice, its activity was, however, compromised with co-administration of the ER stress inhibitor salubrinal. Thus, we suggest that ER stress activation mediates Ginseng Rg3-induced anti-gallbladder cancer cell activity in vitro and in vivo.
Keren Wu, Ning Li, Huaqin Sun, Tao Xu, Fa Jin, Jifeng Nie

1689 related Products with: Endoplasmic reticulum stress activation mediates Ginseng Rg3-induced anti-gallbladder cancer cell activity.

100ug0.25 mL 100ul100ug250 100.00 ug0.1ml (1mg/ml)100ul100ul

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#25950987   2015/05/18 To Up

Polychlorinated biphenyl quinone induces endoplasmic reticulum stress, unfolded protein response, and calcium release.

Organisms are able to respond to environmental insult to maintain cellular homeostasis, which include the activation of a wide range of cellular adaptive responses with tightly controlled mechanisms. The endoplasmic reticulum (ER) is an organelle responsible for protein folding and calcium storage. ER stress leads to the accumulation of unfolded proteins in the ER lumen. To be against or respond to this effect, cells have a comprehensive signaling system, called unfolded protein response (UPR), to restore homeostasis and normal ER function or activate the cell death program. Therefore, it is critical to understand how environmental insult regulates the ingredients of ER stress and UPR signalings. Previously, we have demonstrated that polychlorinated biphenyl (PCB) quinone caused oxidative stress, cytotoxicity, genotoxicity, and apoptosis in HepG2 cells. Here, we investigated the role of a PCB quinone, PCB29-pQ on ER stress, UPR, and calcium release. PCB29-pQ markedly increased the hallmark genes of ER stress, namely, glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein (CHOP) on both protein and mRNA levels in HepG2 cells. We also confirmed PCB29-pQ induced ER morphological defects by using transmission electron microscopy. Moreover, PCB29-pQ induced intracellular calcium accumulation and calpain activity, which were significantly inhibited by the pretreatment of BAPTA-AM (Ca(2+) chelator). These results were correlated with the outcome that PCB29-pQ induces ER stress-related apoptosis through caspase family gene 12, while salubrinal and Z-ATAD-FMK (a specific inhibitor of caspase 12) partially ameliorated this effect, respectively. N-Acetyl-l-cysteine (NAC) scavenged ROS formation and consequently alleviated PCB29-pQ-induced expression of ER stress-related genes. In conclusion, our result demonstrated for the first time that PCB quinone leads to ROS-dependent induction of ER stress, and UPR and calcium release in HepG2 cells, and the evaluation of the perturbations of ER stress, UPR, and calcium signaling provide further information on the mechanisms of PCB-induced toxicity.
Demei Xu, Chuanyang Su, Xiufang Song, Qiong Shi, Juanli Fu, Lihua Hu, Xiaomin Xia, Erqun Song, Yang Song

1966 related Products with: Polychlorinated biphenyl quinone induces endoplasmic reticulum stress, unfolded protein response, and calcium release.

100ul100 100 UG0.05 mg96T1000 TESTS/0.65ml96T96T 100ul100ul 1 mg

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