Brain development is critically dependent on thyroid hormone (T(3)). Krüppel-like factor 9 (Klf9) is a T(3)-inducible gene in developing rat brain, and several lines of evidence support that KLF9 plays a key role in neuronal morphogenesis. Here we extend our findings to the mouse and demonstrate the presence of a functional T(3) response element (T(3)RE) in the 5' flanking region of the mouse Klf9 gene. Klf9 mRNA is strongly induced in the mouse hippocampus and cerebellum in a developmental stage- and T(3)-dependent manner. Computer analysis identified a near optimal direct repeat 4 (DR-4) T(3)RE 3.8 kb upstream of the Klf9 transcription start site, and EMSAs showed that T(3) receptor (TR)-retinoid X receptor heterodimers bound to the T(3)RE with high affinity. The T(3)RE acts as a strong positive response element in transfection assays using a minimal heterologous promoter. In the mouse neuroblastoma cell line N2a[TRbeta1], T(3) caused a dose-dependent up-regulation of Klf9 mRNA. Chromatin immunoprecipitation assays conducted with N2a[TRbeta1] cells showed that TRs associated with the Klf9 T(3)RE, and this association was promoted by T(3). Treatment of N2a[TRbeta1] cells with T(3) led to hyperacetylation of histones 3 and 4 at the T(3)RE site. Furthermore, TRs associated with the DR-4 T(3)RE in postnatal d 4 mouse brain, and histone 4 acetylation was greater at this site compared with other regions of the Klf9 gene. Our study identifies a functional DR-4 T(3)RE located in the mouse Klf9 gene to explain its regulation by T(3) during mammalian brain development.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717889 | PMC |
http://dx.doi.org/10.1210/en.2009-0050 | DOI Listing |
J Neurochem
January 2025
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Misfolding and accumulation of amyloid-β (Aβ) in the brains of patients with Alzheimer's disease (AD) lead to neuronal loss through various mechanisms, including the downregulation of eukaryotic elongation factor 2 (EEF2) protein synthesis signaling. This study investigated the neuroprotective effects of indole and coumarin derivatives on Aβ folding and EEF2 signaling using SH-SY5Y cells expressing Aβ-green fluorescent protein (GFP) folding reporter. Among the tested compounds, two indole (NC009-1, -6) and two coumarin (LM-021, -036) derivatives effectively reduced Aβ misfolding and associated reactive oxygen species (ROS) production.
View Article and Find Full Text PDFBMC Plant Biol
January 2025
Horticulture Department, Faculty of Agriculture, Fayoum University, Fayoum, 63514, Egypt.
Background: The imbalance between Egypt's water requirements and supply necessitates the use of unconventional water sources, such as treated sewage water (TSW) and agricultural drainage water (ADW), to combat water scarcity. This study investigated the effects of foliar glycine betaine (GB) on vegetative growth parameters, physiological characteristics, photosynthetic pigments, leaf element contents, anatomical leaf structures, and antioxidant activity. The experiment was conducted in two successive seasons (2021/2022 and 2022/2023) using Kapok seedlings irrigated with ADW and TSW at different mixing ratios with normal irrigation water (NIW) (25%, 50%, 75%, and 100%), combined with foliar spraying of GB at concentrations of 0.
View Article and Find Full Text PDFClin Proteomics
January 2025
Ophthalmology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli, 1, 00168, Rome, Italy.
Our objective is to determine the protein and complements constituents of Cord blood Platelet-rich plasma (CB-PRP), based on the hypothesis that it contains beneficial components capable of arresting or potentially decelerating the advancement of atrophic age-related macular degeneration (dry-AMD), with the support of radiomics. Two distinct pools of CB-PRP were assessed, each pool obtained from a total of 15 umbilical cord-blood donors. One aliquot of each pool respectively was subjected to proteomic analysis in order to enhance the significance of our findings, by identifying proteins that are shared between the two sample pools and gaining insights into the pathways they are associated with.
View Article and Find Full Text PDFAlcohol Clin Exp Res (Hoboken)
January 2025
Department of Psychiatry, University of California San Diego Medical School, San Diego, California, USA.
Background: Preliminary evaluations of 212 drinking offspring from the San Diego Prospective Study (SDPD) indicated that over 50% developed alcohol use disorder (AUD) by their mid-20s. The present analysis evaluated if those findings remained robust when the group increased to 454 individuals, a sample size that facilitated a search for potential contributors to the high AUD prevalence.
Methods: Semistructured interviews were used to evaluate lifetime AUD diagnoses in 224 daughters and 230 sons from the SDPS (N = 454) by mean age 26.
Proc Natl Acad Sci U S A
January 2025
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!