98%
921
2 minutes
20
Purpose: Changes in extracellular pH occur in the retina and directly affect retinal activity and phototransduction. The authors analyzed the expression in rodent retina of ASIC3, a sensor of extracellular acidosis, and used ASIC3 knockout mice to explore its role in retinal function and survival.
Methods: The expression and the role of ASIC3 were examined by immunolocalization and by comparing retinas from wild-type and knockout mice at different ages through electroretinography, retinal histology (light and electron microscopy), expression of glial fibrillary acidic protein (GFAP), analysis of cell apoptosis (TUNEL assay), and patch-clamp recordings in primary cultures of retinal ganglion cells (RGCs).
Results: ASIC3 is present in the rod inner segment of photoreceptors and in horizontal and some amacrine cells. ASIC3 is also detected in RGCs but does not significantly contribute to ASIC currents recorded in cultured RGCs. At 2 to 3 months, knockout mice experience a 19% enhancement of scotopic electroretinogram a-wave amplitude and a concomitant increase of b-wave amplitude without alteration of retinal structure. Older (8-month-old) knockout mice have 69% and 64% reductions in scotopic a- and b-waves, respectively, and reductions in oscillatory potential amplitudes associated with complete disorganization of the retina and degenerating rod inner segments. GFAP and TUNEL staining performed at 8 and 12 months of age revealed an upregulation of GFAP expression in Müller cells and the presence of apoptotic cells in the inner and outer retina.
Conclusions: Inactivation of ASIC3 enhances visual transduction at 2 to 3 months but induces late-onset rod photoreceptor death, suggesting an important role for ASIC3 in maintaining retinal integrity.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1167/iovs.08-3028 | DOI Listing |
Arterioscler Thromb Vasc Biol
September 2025
Department of Medicine/Division of Cardiology, University of California Los Angeles. (S.S., C.R.S., L.F., M.P., C.P., Z.Z., J.J.M., R.C.D., D.S., A.J.L.).
Background: In genetic studies with the Hybrid Mouse Diversity Panel, we previously identified a chromosome 9 locus for atherosclerosis. We now identify NNMT (nicotinamide -methyltransferase), an enzyme that degrades nicotinamide, as the causal gene in the locus and show that the underlying mechanism involves salvage of nicotinamide to nicotinamide adenine dinucleotide (NAD).
Methods: Gain/loss of function studies in macrophages were performed to examine the role of NAD levels in macrophage proliferation and apoptosis in atherosclerosis.
Mol Cell Biol
September 2025
Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Mammalian cell membranes contain ether lipids, which include an alkyl chain derived from a fatty alcohol that is produced by fatty acyl-CoA reductases (FARs). There are two mammalian FAR genes, and , and mutations in cause the peroxisomal fatty acyl-CoA reductase 1 disorder (PFCRD), which is accompanied by various symptoms, including neurological disorders. To date, the contributions of and to brain ether lipid production and the molecular mechanism of PFCRD have remained unknown.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
September 2025
Integrative Muscle Biology Laboratory, Division of Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Background: Cancer promotes muscle wasting through an imbalance in the tightly regulated protein synthesis and degradation processes. An array of intracellular signalling pathways, including mTORC1 and AMPK, regulate protein synthesis, and these pathways are responsive to the muscle's microenvironment and systemic stimuli. Although feeding and fasting are established systemic regulators of muscle mTORC1 and protein synthesis, the cancer environment's impact on these responses during cachexia development is poorly understood.
View Article and Find Full Text PDFArch Virol
September 2025
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 150069, Harbin, Heilongjiang, China.
Epizootic hemorrhagic disease virus (EHDV) causes severe disease in ruminants. We assessed the pathogenicity of the Chinese EHDV-7 isolate YN09 in mice lacking the type I interferon receptor and in sheep. In mice, YN09 infection resulted in 100% mortality, with histopathological lesions, viral replication, and immunoreactivity in multiple organs.
View Article and Find Full Text PDFNat Commun
September 2025
Centre for Genomics and Oncological Research (GENYO), Avenue de la Ilustración 114, 18016, Granada, Spain.
Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its negative regulators PER and CRY. Although circadian rhythms and CLOCK protein are mostly absent during embryogenesis, the lack of BMAL1 during prenatal development causes an early aging phenotype during adulthood, suggesting that BMAL1 performs an unknown non-circadian function during organism development that is fundamental for healthy adult life. Here, we show that BMAL1 interacts with TRIM28 and facilitates H3K9me3-mediated repression of transposable elements in naïve pluripotent cells, and that the loss of BMAL1 function induces a widespread transcriptional activation of MERVL elements, 3D genome reorganization and the acquisition of totipotency-associated molecular and cellular features.
View Article and Find Full Text PDF