AI Article Synopsis
- Reactive oxygen species (ROS), specifically superoxide anions and hydrogen peroxide, contribute to liver cell death, with menadione and H2O2 used to study their effects in primary hepatocyte cultures.
- Menadione triggers apoptosis through JNK activation and caspase pathways, while H2O2 leads to necrotic cell death at high concentrations, without activating MAPK signaling.
- Superoxide dismutase (PEG-SOD) can prevent apoptosis from menadione, indicating that managing oxidative stress might protect liver cells from damage.
Article Abstract
Background/aims: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of hepatocytes were exposed to the superoxide anion donor menadione (10-50 micromol/L) or H2O2 (1-5 mmol/L). Hepatocytes were also treated with caspases and MAPKs inhibitors, superoxide dismutase (PEG-SOD) and SNAP, a nitric oxide donor. Apoptosis was determined by measuring caspase-9, -6, -3 activation and cleaved PARP, and necrotic cell death by Sytox Green staining.
Results: (1) Menadione (50 micromol/L) induces JNK phosphorylation, caspase-9, -6, -3 activation, PARP cleavage and apoptosis. Superoxide anions-induced apoptosis is dependent on JNK activity. Menadione (50 micromol/L) induces the phosphorylation of ERK1/2 and this attenuates cell death. (2) H2O2 increases necrotic cell death at high concentration or when H2O2 detoxification is impaired. H2O2 does not activate MAPKs signalling. (3) PEG-SOD prevents ERK1/2-, JNK- phosphorylation, caspase activation and apoptosis induced by menadione. Glutathione depletion increases menadione-induced apoptosis. (4) SNAP abolishes menadione-induced apoptosis but increases necrotic cell death.
Conclusions: In normal hepatocytes, superoxide anions-induced caspase activation and apoptosis is dependent on JNK activity and totally abolished by superoxide scavengers.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jhep.2005.07.034 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
controls wing developmental growth by targeting .
Anim Cells Syst (Seoul)
December 2024
School of Systems Biomedical Science, Soongsil University, Seoul, Republic of Korea.
Tissue growth is controlled by various signaling pathways, such as the insulin/IGF-signaling (IIS) pathway. Although IIS activation is regulated by a complex regulatory network, the mechanism underlying miRNA-based regulation of the IIS pathway in wing development remains unclear. In this study, we found that the wing size of adult flies was negatively affected by miR-263b expression.
View Article and Find Full Text PDFNeurotrophomodulatory effect of TNF-α through NF-κB in rat cortical astrocytes.
Cytotechnology
February 2025
Division of Neurobiology, Department of Zoology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat India.
Tumor necrosis factor alpha (TNF-α) is a well-known pro-inflammatory cytokine originally recognized for its ability to induce apoptosis and cell death. However, recent research has revealed that TNF-α also plays a crucial role as a mediator of cell survival, influencing a wide range of cellular functions. The signaling of TNF-α is mediated through two distinct receptors, TNFR1 and TNFR2, which trigger various intracellular pathways, including NF-κB, JNK, and caspase signaling cascades.
View Article and Find Full Text PDFMitochondrial dysfunction in pancreatic acinar cells: mechanisms and therapeutic strategies in acute pancreatitis.
Front Immunol
December 2024
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Acute pancreatitis (AP) is an inflammatory disease of the pancreas and a complex process involving multiple factors, with mitochondrial damage playing a crucial role. Mitochondrial dysfunction is now considered a key driver in the development of AP. This dysfunction often presents as increased oxidative stress, altered membrane potential and permeability, and mitochondrial DNA damage and mutations.
View Article and Find Full Text PDFCrosstalk between thyroid CSCs and immune cells: basic principles and clinical implications.
Front Immunol
December 2024
The Seventh Department of General Surgery, Department of Thyroid Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
Thyroid cancer has become the most common endocrine malignancy. Although the majority of differentiated thyroid cancers have a favorable prognosis, advanced thyroid cancers, iodine-refractory thyroid cancers, and highly malignant undifferentiated carcinomas still face a serious challenge of poor prognosis and even death. Cancer stem cells are recognized as one of the central drivers of tumor evolution, recurrence and treatment resistance.
View Article and Find Full Text PDFMonitoring of cancer ferroptosis with [F]hGTS13, a system xc- specific radiotracer.
Theranostics
January 2025
Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, 94305, USA.
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, characterized by resistance to conventional therapies and poor survival. Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic target for GBM treatment. However, there are currently no non-invasive imaging techniques to monitor the engagement of pro-ferroptotic compounds with their respective targets, or to monitor the efficacy of ferroptosis-based therapies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!