Sodium sulfite (SS) is a biological derivative of the air pollutant sulfur dioxide, and is often used as a food and pharmaceutical additive. Improper or excessive SS exposure in liver cell death. The phenomenon of simultaneous regulation of apoptosis, necroptosis, and pyroptosis is defined as PANoptosis. However, the specific types of programmed cell death (PCD) caused by SS and their interconnections remain unclear. In the present study, C57BL/6 mice were orally administered SS for 30 d, consecutively, to establish an in vivo mouse exposure model. AML-12 cells were treated with SS for 24 h to establish an in vitro exposure model. The results showed that SS-induced mitochondrial reactive oxygen species (mtROS) accumulation activated the BAX/Bcl-2/caspase 3 pathway to trigger apoptosis and RIPK1/RIPK3/p-MLKL to trigger necroptosis. Interestingly, ROS-activated p-MLKL perforated not the cell membrane as well as the lysosomal membrane. We determined that p-MLKL mediates lysosomal membrane permeabilization (LMP), resulting in cathepsin B (CTSB) release. Furthermore, knockdown of MLKL, a CTSB inhibitor (CA074-ME) and an NLRP3 inhibitor (MCC950) alleviated SS-induced pyroptosis. In summary, our study showed that SS induced apoptosis and necroptosis though mtROS accumulation, whereas the activation of p-MLKL mediated NLRP3-dependent pyroptosis by causing CTSB leakage through LMP. This study comprehensively explored the mechanism unerlying SS-induced PCD and provided an experimental basis for p-MLKL as a potential regulatory protein in PANoptosis.
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http://dx.doi.org/10.1016/j.jhazmat.2024.133719 | DOI Listing |
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread immune dysregulation that affects multiple organ systems, including the skin and cardiovascular system. The crosstalk between different cell death pathways-such as apoptosis, necroptosis, and neutrophil extracellular trap (NETosis), plays a pivotal role in the pathogenesis of SLE, influencing both cutaneous and cardiac manifestations. Cutaneous lupus erythematosus (CLE) is one of the most common early signs of SLE, affecting up to 80% of patients.
View Article and Find Full Text PDFCell Death Dis
January 2025
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China.
UVB irradiation induces diverse modalities of regulatory cell death in keratinocytes. Recently, the pattern of coexistence of pyroptosis, apoptosis, and necroptosis has been termed PANoptosis; however, whether PANoptosis occurs in keratinocytes in UVB-induced skin injury remains unclear. We observed that the key molecules of GSDMD-mediated pyroptosis, apoptosis, and necroptosis, which are N-terminal GSDMD, cleaved caspase-3/PARP, and phosphorylated MLKL, respectively, were elevated in keratinocytes of UVB-challenged mice and human skin tissue.
View Article and Find Full Text PDFPathogens
January 2025
Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
PANoptosis is a newly identified programmed cell death pathway that integrates characteristics of apoptosis, pyroptosis, and necroptosis. It plays a dual role in the host immune response to bacterial infections. On one hand, PANoptosis acts as a protective mechanism by inducing the death of infected cells to eliminate pathogens and releasing pro-inflammatory cytokines to amplify the immune response.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Fisheries Science Institute, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100068, China.
Goldfish (), subjected to millennia of artificial selection and breeding, have diversified into numerous ornamental varieties, such as the celestial-eye (CE) goldfish, noted for its unique dorsal eye rotation. Previous studies have primarily focused on anatomical modifications in CE goldfish eyes, yet the molecular underpinnings of their distinctive eye orientation remain poorly understood. This study employed high-throughput transcriptome and proteome sequencing on 110-day-old full-sibling CE goldfish, which displayed either anterior or upward eye rotations.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Early diagnosis and disease management based on risk stratification have a very positive impact on colon adenocarcinoma (COAD) prognosis. It is of positive significance to further explore risk stratification of COAD patients and identify predictive molecular biomarkers. PANoptosis is defined as a form of inflammatory cell death regulated by PANoptosome, with common features of pyroptosis, apoptosis and necroptosis.
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