To evaluate hepatoprotective effect of alpha-calcitonin gene-related peptide (alphaCGRP), we compared the susceptibilities of alphaCGRP-/- and wild-type mice to concanavalin A (Con A)-induced hepatitis. Twelve hours after Con A administration, serum transaminases were markedly higher in alphaCGRP-/- than wild-type mice, and much more extensive TUNEL-positive lesions and DNA fragmentation were detected in the livers of alphaCGRP-/- mice. Notably, expression of IL-6 was selectively diminished in alphaCGRP-/- mice, suggesting that induction of IL-6 during acute inflammatory responses is blunted in alphaCGRP-/- mice. In addition, primary cultured alphaCGRP-/- hepatocytes were more susceptible to IFN-gamma-induced cell death than hepatocytes from wild-type mice. Administration of exogenous alphaCGRP reduced the incidence of apoptosis among hepatocytes and endothelial cells. It thus appears that alphaCGRP exerts a hepatoprotective effect by modulating cytokine expression and preventing apoptosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2006.02.132 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Protection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.
Blood
January 2025
Cleveland Clinic, Cleveland, Ohio, United States.
Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.
View Article and Find Full Text PDFMHC Class II-Expressing Mucosal Mast Cells Promote Intestinal Mast Cell Hyperplasia in a Mouse Model of Food Allergy.
Allergy
January 2025
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Background: IgE-mediated food allergy is accompanied by mucosal mast cell (MMC) hyperplasia in the intestinal mucosa. Intestinal MMC numbers correlate with the severity of food allergy symptoms. However, the mechanisms by which MMCs proliferate excessively are poorly understood.
View Article and Find Full Text PDFKnock-out mouse models and single particle ICP-MS reveal that SP-D and SP-A deficiency reduces agglomeration of inhaled gold nanoparticles in vivo without significant changes to overall lung clearance.
Nanotoxicology
January 2025
Infection, Inflammation and Repair, Faculty of Medicine, University of Southampton, Southampton, UK.
The role of surfactant proteins A and D (SP-A and SP-D) in lung clearance and translocation to secondary organs of inhaled nanoparticles was investigated by exposing SP-A and SP-D knockout (AKO and DKO) and wild type (WT) mice nose-only for 3 hours to an aerosol of 20 nm gold nanoparticles (AuNPs). Animals were euthanised at 0-, 1-, 7- and 28-days post-exposure. Analysis by inductively coupled plasma mass spectrometry (ICP-MS) of the liver and kidneys showed that extrapulmonary translocation was below the limits of detection.
View Article and Find Full Text PDFLIG1 is a synthetic lethal target in BRCA1 mutant cancers.
Mol Cancer Ther
January 2025
Tango Therapeutics (United States), Boston, United States.
Synthetic lethality approaches in BRCA1/2-mutated cancers have focused on poly(ADP-ribose) polymerase (PARP) inhibitors, which are subject to high rates of innate or acquired resistance in patients. Here, we used CRISPR/Cas9-based screening to identify DNA Ligase I (LIG1) as a novel target for synthetic lethality in BRCA1-mutated cancers. Publicly available data supported LIG1 hyperdependence of BRCA1-mutant cells across a variety of breast and ovarian cancer cell lines.
View Article and Find Full Text PDFUnlabelled: Autism Spectrum Disorder (ASD) is characterized by restricted and repetitive behaviors and social differences, both of which may manifest, in part, from underlying differences in corticostriatal circuits and reinforcement learning. Here, we investigated reinforcement learning in mice with mutations in either or , both high-confidence ASD risk genes associated with major syndromic forms of ASD. Using an odor-based two-alternative forced choice (2AFC) task, we tested adolescent mice of both sexes and found male and heterozygote (Het) mice showed enhanced learning performance compared to their wild type (WT) siblings.
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!