Department of Human Nutrition and Hospitality Management

Permanent URI for this community

https://ir.ua.edu/handle/123456789/59

Browse

Browsing Department of Human Nutrition and Hospitality Management by Subject "ACTIVATION"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL
    (Pergamon, 2022) Park, Han-A; Crowe-White, Kristi M.; Ciesla, Lukasz; Scott, Madison; Bannerman, Sydni; Davis, Abigail U.; Adhikari, Bishnu; Burnett, Garrett; Broman, Katheryn; Ferdous, Khondoker Adeba; Lackey, Kimberly H.; Licznerski, Pawel; Jonas, Elizabeth A.; University of Alabama Tuscaloosa; Yale University
    Alpha-tocotrienol ( a-TCT) is a member of the vitamin E family. It has been reported to protect the brain against various pathologies including cerebral ischemia and neurodegeneration. However, it is still unclear if a-TCT exhibits beneficial effects during brain development. We hypothesized that treatment with a-TCT improves intracellular redox homeostasis supporting normal development of neurons. We found that primary hippocampal neurons isolated from rat feti grown in a-TCT-containing media achieved greater levels of neurite complexity compared to ethanol-treated control neurons. Neurons were treated with 1 mu M aTCT for 3 weeks, and media were replaced with fresh a-TCT every week. Treatment with a-TCT increased a-TCT levels (26 pmol/mg protein) in the cells, whereas the control neurons did not contain a-TCT. a-TCT-treated neurons produced adenosine triphosphate (ATP) at a higher rate and increased ATP retention at neurites, supporting formation of neurite branches. Although treatment with a-TCT alone did not change neuronal viability, neurons grown in a-TCT were more resistant to death at maturity. We further found that messenger RNA and protein levels of B-cell lymphoma-extra large (Bcl-xL) are increased by a-TCT treatment without inducing posttranslational cleavage of Bcl-xL. Bcl-xL is known to enhance mitochondrial energy production, which improves neuronal function including neurite out-growth and neurotransmission. Therefore alpha-TCT-mediated Bcl-xL upregulation may be the central mechanism of neuroprotection seen in the alpha-TCT-treated group. In summary, treat-ment with alpha-TCT upregulates Bcl-xL and increases ATP levels at neurites. This correlates with increased neurite branching during development and with protection of mature neu-rons against oxidative stress. (C) 2022 Elsevier Inc. All rights reserved.
  • Thumbnail Image
    Item
    FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells
    (Frontiers, 2018) Krick, Stefanie; Helton, Eric Scott; Hutcheson, Samuel B.; Blumhof, Scott; Garth, Jaleesa M.; Denson, Rebecca S.; Zaharias, Rennan S.; Wickham, Hannah; Barnes, Jarrod W.; University of Alabama Birmingham; University of Alabama Tuscaloosa
    The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of proteins. The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation. In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase C gamma (PLC gamma)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Here, we demonstrate that FGF23 increased the O-GlcNAc modification of proteins in HBECs. Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6). Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects. Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs. These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs. The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.