Macroautophagy is an evolutionary conserved lysosomal pathway involved in the turnover of cellular macromolecules and organelles. In spite of its essential role in tissue homeostasis, the molecular mechanisms regulating mammalian macroautophagy are poorly understood. Here, we demonstrate that a rise in the free cytosolic calcium ([Ca(2+)](c)) is a potent inducer of macroautophagy. Various Ca(2+) mobilizing agents (vitamin D(3) compounds, ionomycin, ATP, and thapsigargin) inhibit the activity of mammalian target of rapamycin, a negative regulator of macroautophagy, and induce massive accumulation of autophagosomes in a Beclin 1- and Atg7-dependent manner. This process is mediated by Ca(2+)/calmodulin-dependent kinase kinase-beta and AMP-activated protein kinase and inhibited by ectopic Bcl-2 located in the endoplasmatic reticulum (ER), where it lowers the [Ca(2+)](ER) and attenuates agonist-induced Ca(2+) fluxes. Thus, an increase in the [Ca(2+)](c) serves as a potent inducer of macroautophagy and as a target for the antiautophagy action of ER-located Bcl-2.
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http://dx.doi.org/10.1016/j.molcel.2006.12.009 | DOI Listing |
Nat Commun
January 2025
Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China.
Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone have been identified as tumor suppressors. However, their roles in virus infection remain unclear. Here, we demonstrate that PBLD upregulates the type I interferon (IFN-I) response through activating NF-kappaB (NF-κB) signaling pathway to resist viral infection in cells and mice.
View Article and Find Full Text PDFInflamm Res
January 2025
Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing, 100084, China.
Background: Traditional Chinese medicine (TCM) is a valuable resource for drug discovery and has demonstrated excellent efficacy in treating inflammatory diseases. This study aimed to develop a universal gene signature-based strategy for high-throughput discovery of anti-inflammatory drugs, especially Traditional Chinese medicine (TCM).
Methods: The disease gene signature of liposaccharide-stimulated THP-1 cells and drug gene signatures of 655 drug candidates were established via sequencing.
EMBO J
December 2024
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
The cytosolic nucleic acid sensors RIG-I and cGAS induce type-I interferon (IFN)-mediated immune responses to RNA and DNA viruses, respectively. So far no connection between the two cytosolic pathways upstream of IKK-like kinase activation has been investigated. Here, we identify heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a positive regulator of IRF3 phosphorylation and type-I IFN induction downstream of both cGAS and RIG-I.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
September 2024
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.
This study aims to investigate the effect of essential oil of Acori Tatarinowii Rhizoma on microglial pyroptosis and decipher the underlying mechanism. BV-2 cells were treated with 1 μg·mL~(-1) lipopolysaccharide(LPS) and 10 μmol·L~(-1) nigericin sodium salt for the modeling of pyroptosis. The cells were treated with different doses of essential oil of Acori Tatarinowii Rhizoma, and then the cell viability and apoptosis were examined by the CCK-8 assay and flow cytometry, respectively.
View Article and Find Full Text PDFMol Metab
December 2024
Division of Neurodegenerative Disorders, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, Canada; Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. Electronic address:
Objective: Antagonism of the muscarinic acetylcholine type 1 receptor (MR) promotes sensory axon repair and is protective in peripheral neuropathy, however, the mechanism remains elusive. We investigated the role of the heat-sensing transient receptor potential melastatin-3 (TRPM3) cation channel in MR antagonism-mediated nerve regeneration and explored the potential of TRPM3 activation to facilitate axonal plasticity.
Methods: Dorsal root ganglion (DRG) neurons from adult control or diabetic rats were cultured and treated with TRPM3 agonists (CIM0216, pregnenolone sulfate) and MR antagonists pirenzepine (PZ) or muscarinic toxin 7 (MT7).
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