Human Polyclonal RIPK1 Ab
- Known as:
- Human Polyclonal RIPK1 Antibody
- Catalog number:
- a7414
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- ABclonal
- Gene target:
- Human Polyclonal RIPK1
Related genes to: Human Polyclonal RIPK1 Ab
- Gene:
- RIPK1 NIH gene
- Name:
- receptor interacting serine/threonine kinase 1
- Previous symbol:
- -
- Synonyms:
- RIP
- Chromosome:
- 6p25.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-07
- Date modifiied:
- 2015-11-17
Related products to: Human Polyclonal RIPK1 Ab
Related articles to: Human Polyclonal RIPK1 Ab
- This study aimed to investigate whether Huangqi Chongteng Yin(HQCTY) alleviates oxygen-glucose deprivation/reoxygenation(OGD/R)-induced injury and mitochondrial dysfunction in mouse hippocampal HT22 neurons by modulating the receptor-interacting protein kinase 1(RIPK1)/receptor-interacting protein kinase 3(RIPK3)/mixed lineage kinase domain-like protein(MLKL)-mediated necroptosis signaling pathway. After preparing HQCTY-containing serum and verifying its safety and efficacy, HT22 cells were divided into the control group, OGD/R group, HQCTY-containing serum low-, medium-, and high-dose groups(5%, 10%, and 20%), and an edaravone(Eda) group. Cell viability and membrane damage were assessed using the cell counting kit-8(CCK-8) assay and lactate dehydrogenase(LDH) release assays, respectively, while nuclear morphology was evaluated by DAPI staining. The expression and phosphorylation levels of RIPK1, RIPK3, and MLKL were detected by Western blot, and the expression and subcellular localization of MLKL and phosphorylated(p)-MLKL were examined by immunofluorescence assay. Mitochondrial membrane potential, energy metabolism, mitochondrial network morphology, and ultrastructural alterations were evaluated using JC-1 staining, ATP assay kit, Mito-Tracker Green staining, and transmission electron microscopy, respectively. In addition, fluorescence staining was performed to assess the morphology of translocase of outer mitochondrial membrane 20(TOM20) and the cytoskeleton(phalloidin staining). The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6, and IL-18 were determined by ELISA. The results showed that, compared with the OGD/R group, HQCTY significantly increased HT22 cell viability, reduced LDH release and nuclear condensation, markedly downregulated the protein expression of p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLKL, while ameliorating the abnormal localization of p-MLKL. Furthermore, HQCTY significantly improved mitochondrial membrane potential, increased ATP production, and promoted the restoration of mitochondrial network and ultrastructure. It also significantly reduced the levels of TNF-α, IL-1β, IL-6, and IL-18. These findings indicate that HQCTY may directly protect neurons from OGD/R injury by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis signaling pathway and improving mitochondrial structure and energy metabolism, thereby providing new insights and intervention strategies for the application of traditional Chinese medicine formulas in neuroprotection after cerebral ischemia-reperfusion injury. - Source: PubMed
Liu KanHe Meng-HaoFu Xin-YingZeng YangZhu Xin-HuaYao Xin-Yan - Tumour necrosis factor (TNF) is a pleiotropic cytokine originally identified for its ability to kill cancer cells. However, a paradoxical tumour-promoting role for TNF emerged when early attempts to exploit its anti-tumour activity in cancer therapy produced conflicting outcomes, raising the question of whether TNF should be viewed as a therapeutic agent or a treatment target in cancer. Here, we demonstrate that expression of cFLIP, a catalytically inactive paralogue of caspase-8 (CASP8), determines the susceptibility of melanoma cells to TNF and thereby controls melanoma growth in a syngeneic, immune-competent mouse model of B16F10 cutaneous melanoma. B16F10 melanoma cells lacking cFLIP (cFlip cells) failed to grow in wild-type mice, whereas in TNF-deficient mice, cFlip melanoma cells formed palpable tumours and exhibited robust subcutaneous growth. These findings indicate that TNF alone is sufficient to control melanoma growth in the absence of cFLIP. Importantly, the anti-tumour activity of TNF has predominantly been investigated through targeting cellular inhibitors of apoptosis proteins (cIAPs), which promotes RIPK1 activation and TNF-induced cytotoxicity. We show that genomic ablation of cIAPs or RIPK1, in contrast to cFLIP, neither triggered TNF-induced toxicity nor affected melanoma growth in vivo. Collectively, our data underscore the central role of cFLIP in regulating melanoma responses to TNF and suggest that endogenous immune surveillance as well as immunotherapies involving TNF could strongly benefit from cFLIP targeting strategies. - Source: PubMed
Publication date: 2026/08/01
Stachelscheid JohannaKaul CäciliaGerstenberg KatrinWerthenbach J PaulSchorn FabianSteinkamp JoyZigrino PaolaPasparakis ManolisSchiffmann Lars MKashkar Hamid - Licoricidin (LCD), a natural isoflavonoid compound extracted from Glycyrrhiza species, has been extensively demonstrated to possess diverse biological activities, including anti-inflammatory and potent anti-cancer effects. However, the precise mechanism underlying LCD action against hepatocellular carcinoma (HCC) remains unclear, particularly regarding its regulation of cell death. In this study, we comprehensively explored the effects of LCD on HCC cells and investigated its role and mechanism of action in the induction of PANoptosis. Our results reveal that LCD exhibited potent anti-HCC activities by decreasing cell viability and significantly inhibiting clonogenic survival in HCC cell lines. Our results demonstrate that LCD triggered a substantial accumulation of reactive oxygen species and induced depolarization of the mitochondrial membrane, leading to profound mitochondrial dysfunction. We further confirmed that LCD activated a comprehensive PANoptosis program by synchronously upregulating the expression of apoptotic proteins (Bax, c-CASP3, and c-PARP1), pyroptotic proteins (c-CASP 1 and c-GSDMD), and the phosphorylation of necroptotic executioners (p-MLKL and p-RIPK1). Treatment with the ROS inhibitor (NAC), apoptosis inhibitor (ZVAD), or necroptosis inhibitor (Nec-1) significantly reduced the expression of PANoptosis-related proteins in LCD-treated cells. Furthermore, molecular docking simulations and cellular thermal shift assay (CETSA) assay confirmed the direct and stable binding of LCD to PANoptosis-related proteins. In summary, we show for the first time that LCD exerts favorable anti-HCC activities via the induction of PANoptosis through a ROS-dependent mechanism and potntial direct modulation of core executive proteins. This multi-target action suggests that LCD could be a novel candidate for the management of hepatocellular carcinoma. - Source: PubMed
Publication date: 2026/07/13
Hung Ming-ChunChiou Hui-LingHsieh Yi-HsienChen Pei-NiYu Yung-LuenLee Hsiang-Lin - Recurrence and metastasis are the leading causes of mortality in renal cell carcinoma (RCC), and its intrinsic drug resistance further limits effective therapeutic options. Synergistic activation of multiple regulated cell death pathways has recently emerged as a novel approach to overcome therapeutic resistance. Here, we developed two mitochondria-targeted iridium(III) photosensitizers, Ir-MT1 and Ir-MT2, for synergistic photoimmunotherapy of RCC. Upon white-light irradiation, Ir-MT1/2 induced severe mitochondrial damage and dysfunction, leading to massive release of mitochondrial contents. Mitochondrial DNA leakage activated the cGAS-stimulator of interferon genes pathway and caspase-1-mediated pyroptosis cascade, whereas excessive Ca efflux promoted RIPK1/RIPK3 phosphorylation and induced necroptosis. These death signals facilitated pore formation by gasdermin D and mixed lineage kinase domain-like protein in the plasma membrane, resulting in membrane rupture, release of damage-associated molecular patterns, and immunogenic cell death synergistically. In vivo, Ir-MT1/2 not only effectively suppressed primary tumor growth but also eliminated distant tumors through activation of anti-tumor immunity, exhibiting potent therapeutic efficacy and favorable biosafety. Overall, our work provides the evidence that a single iridium complex can simultaneously trigger pyroptosis-necroptosis synergy, overcoming intrinsic drug resistance and offering a promising strategy for multi-network systemic therapy of RCC. - Source: PubMed
Publication date: 2026/07/28
Qin XinChen Meng-DiGao WenqiWang YipingLiu Lin-QingTeng ZhenQi TienanWang QiyuanWang YuxuanLi DaoxiangYan KeqiangPan LingZhao ZhongweiZhao ShuoWang Kang-NanFu ShuaiYu Nengwang - Cell death is a key effector mechanism of the innate immune system for host defense. While it is beneficial for pathogen clearance, excess lytic cell death is linked to inflammation, pathology, and disease. Therefore, tight regulation of cell death execution is critical. PANoptosis is an innate immune, lytic, and inflammatory cell death pathway initiated by innate immune sensors and driven by caspases and RIPKs, with roles in infection, inflammatory disease, and cancer. During PANoptosis, caspases and RIPKs within PANoptosome complexes activate multiple executioner proteins, including gasdermin (GSDM) family proteins and mixed lineage kinase domain-like pseudokinase (MLKL). These executioners form membrane pores that lead to membrane lysis and the release of DAMPs and cytokines. Although multiple executioners are activated during PANoptosis, the requirement for individual executioners in driving the lytic cell death remains unclear. To address this, we performed a comprehensive genetic analysis of GSDMD, GSDME, and MLKL using single, double, and triple knockout primary macrophages across triggers known to activate distinct PANoptosomes. Deletion of individual executioners did not reduce the activation of caspases or other executioners and did not fully block PANoptosis, suggesting these executioner molecules often act in a compensatory manner to execute PANoptosis. Furthermore, combined deletion of all three executioners provided greater protection than any single or double deletion. However, residual cell death still occurred even after genetic deletion of all three executioner proteins, suggesting the involvement of additional executioners that remain to be identified. Overall, our study suggests that targeting individual executioners will not be sufficient in disease contexts where PANoptosis drives pathology, and targeting the full executioner network or upstream molecules, such as sensors or essential PANoptosome complex components, will be needed for therapeutic efficacy in infection, inflammatory disease, and cancer. - Source: PubMed
Publication date: 2026/07/28
Indari OmkarGiri PrashantTweedell Rebecca EKanneganti Thirumala-Devi