Pahutoxin (PHN) is a long chain detergent-like quaternary ammonium cationic substance derived from defensive skin secretions of trunkfish. A recent study has revealed that PHN's ichthyotoxicity and its phospholipid membrane disruption effect are produced by two separate mechanisms, which presumably represent two separate physicochemical domains in the PHN molecule [Kalmanzon, E., Rahamim, Y., Barenholz, Y., Carmeli, S., Zlotkin, E., 2003. Receptor-mediated toxicity of pahutoxin, a marine trunkfish surfactant. Toxicon 42, 63-71]. Here we report on the occurrence of a natural endogenous mechanism, which regulates the above PHN's functional duality. The regulation is performed by the aid of two separates constituents of the trunkfish secretion, which either selectively amplify PHN's ichthyotoxicity (factor I) or suppress its phospholipids permeabilization effect (factor II). The ecological significance of such endogenous regulation is discussed.
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http://dx.doi.org/10.1016/j.toxicon.2004.07.029 | DOI Listing |
Zh Nevrol Psikhiatr Im S S Korsakova
December 2024
Kazan (Volga region) Federal University, Kazan, Russia.
Cerebrovascular diseases themselves are the second most common cause of cognitive impairment (dementia). In addition, cerebral small vessel disease (CSVD) makes a significant contribution to the clinical picture of neurodegenerative diseases. Since there are currently no pharmacological treatments for CSVD, a promising method is the activation of the endogenous mechanisms of sanogenesis.
View Article and Find Full Text PDFBMC Plant Biol
December 2024
Tea Research Institute, Anhui Academy of Agricultural Sciences, Huangshan, 245000, China.
Background: Adventitious root (AR) formation is the key step for successful cutting propagation of tea plants (Camellia sinensis L.). Studies showed that arbuscular mycorrhizal fungus (AMF) can promote the rooting ability, and auxin pathway in basal stem of cuttings was involved in this process.
View Article and Find Full Text PDFNat Commun
December 2024
Experimental Medicine & Immunotherapeutics, University of Cambridge, Cambridge, UK.
We describe a structural and functional study of the G protein-coupled apelin receptor, which binds two endogenous peptide ligands, apelin and Elabela/Toddler (ELA), to regulate cardiovascular development and function. Characterisation of naturally occurring apelin receptor variants from the UK Genomics England 100,000 Genomes Project, and AlphaFold2 modelling, identifies T89 as important in the ELA binding site, and R168 as forming extensive interactions with the C-termini of both peptides. Base editing to introduce an R/H168 variant into human stem cell-derived cardiomyocytes demonstrates that this residue is critical for receptor binding and function.
View Article and Find Full Text PDFCancer Genomics Proteomics
December 2024
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Background/aim: Treatment with retinoic acid (RA) often promotes neuroblastoma differentiation and growth inhibition, including the suppression of the expression of the MYCN oncogene. However, RA also targets protumoral chemokines, such as CCL2, which may contribute to the development of resistance. The present study aimed to investigate the regulation and function of CCL2 and N-Myc in RA-treated neuroblastoma cells.
View Article and Find Full Text PDFCancer Cell
December 2024
Genome Institute of Singapore, Agency for Science, Technology, and Research (A(∗)STAR), 60 Biopolis Street, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore. Electronic address:
Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify P4HA1, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8 T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion.
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