RIP1 and RIP3 are necroptosis initiators, but their roles in regulation of glycolysis remain elusive. In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA. Moreover, shikonin also triggered accumulation of intracellular HO and depletion of GSH and cysteine. Mitigation of intracellular HO via supplement of GSH reversed shikonin-induced glycolysis suppression. The role of intracellular HO in regulation of glycolysis suppression was further confirmed in the cells treated with exogenous HO. Notably, inhibition of RIP1 or RIP3 prevented intracellular HO accumulation, which was correlated with preventing shikonin-induced downregulation of x-CT and depletion of GSH and cysteine. In addition, supplement of pyruvate effectively inhibited shikonin- or exogenous HO-induced accumulation of intracellular HO and glioma cell death. Taken together, we demonstrated in this study that RIP1 and RIP3 contributed to shikonin-induced glycolysis suppression via increasing intracellular HO.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.canlet.2018.03.046 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Analysis of MLKL, RIP1 and RIP3 Immunostaining Markers in Human Liver Tissue from Fatal Yellow Fever Cases: Insights into Necroptosis.
Viruses
December 2024
Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.
Necroptosis is a regulated form of cell death implicated in several pathological conditions, including viral infections. In this study, we investigated the expression and correlation of necroptosis markers MLKL, RIP1 and RIP3 in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). The liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture.
View Article and Find Full Text PDFFGF20 promotes spinal cord injury repair by inhibiting the formation of necrotic corpuscle P-MLKL/P-RIP1/P-RIP3 in neurons.
J Cell Mol Med
December 2024
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
The disruption of the local microenvironment subsequent to spinal cord injury (SCI) leads to a substantial loss of neurons in the affected region, which is a major contributing factor to impaired motor function recovery in patients. Fibroblast growth factor 20 (FGF20) is a neurotrophic factor that plays a crucial role in neuronal development and homeostasis. In this study, the recombinant human FGF20 (rhFGF20) was found to mitigate the process of necroptosis in a mouse model of SCI, thereby reducing neural functional deficits and promoting SCI repair.
View Article and Find Full Text PDFInvolvement of necroptosıs and apoptosıs ın protectıve effects of cyclosporın a on ischemıa-reperfusıon injury in rat kıdney.
J Mol Histol
December 2024
Department of Pharmacology, School of Medicine, Uskudar University, Istanbul, Turkey.
Article Synopsis
- The study examined how low dose cyclosporin A (CsA) can protect rat kidneys from damage caused by ischemia-reperfusion (IR) injury, focusing on mechanisms of cell death.
- Three groups were tested: a control group, an IR group (exposed to restricted blood flow), and an IR + CsA group (received CsA before the IR procedure).
- Results showed that CsA significantly improved kidney function and reduced injury markers compared to the IR group, indicating its protective effects against IR-related kidney damage.
TBBPA caused multiple intestinal injuries via ROS/NF-κB signal in common carp.
Aquat Toxicol
December 2024
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:
Tetrabromobisphenol A (TBBPA) is an aquatic environment's prevalent pollutant, posing a great threat to the health of aquatic animals. The intestine is a key organ for nutrient absorption as well as an important barrier to prevent pollutants from invading the body of fish. Exploring the effects of pollutants on the intestine is of great significance for maintaining fish health.
View Article and Find Full Text PDFTrimethylamine Induced Chronic Kidney Injury by Activating the ZBP1-NLRP3 Inflammasome Pathway.
Physiol Res
November 2024
Department of Physiology, Hebei Medical University, Shijiazhuang, China. Hebei Provincial Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.
Trimethylamine N-oxide (TMAO), a bioactive metabolite of gut microbes, plays a pivotal role in the pathogenesis of kidney diseases by activating programmed cell death (PCD) pathways. However, whether trimethylamine (TMA) contributes to chronic kidney injury and which kind of PCD is involved in TMA-induced chronic kidney injury has not been previously evaluated. To observe the effect of TMA, male C57BL/6J mice were randomly divided into two groups: the Control group and the TMA group.
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!