Age-related bone loss is associated with decreased bone formation, increased bone resorption, and accumulation of bone marrow fat. During aging, differentiation potential of bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) is shifted toward an adipogenic lineage and away from an osteogenic lineage. In aged bone tissue, we previously observed pathological opening of the mitochondrial permeability transition pore (MPTP) which leads to mitochondrial dysfunction, oxidative phosphorylation uncoupling, and cell death. Cyclophilin D (CypD) is a mitochondrial protein that facilitates opening of the MPTP. We found earlier that CypD is downregulated during osteogenesis of BMSCs leading to lower MPTP activity and, thus, protecting mitochondria from dysfunction. However, during adipogenesis, a fate alternative to osteogenesis, the regulation of mitochondrial function and CypD expression is still unclear. In this study, we observed that BMSCs have increased CypD expression and MPTP activity, activated glycolysis, and fragmented mitochondrial network during adipogenesis. Adipogenic C/EBPα acts as a transcriptional activator of expression of the CypD gene, Ppif, during this process. Inflammation-associated transcription factor NF-κB shows a synergistic effect with C/EBPα inducing Ppif expression. Overall, we demonstrated changes in mitochondrial morphology and function during adipogenesis. We also identified C/EBPα as a transcriptional activator of CypD. The synergistic activation of CypD by C/EBPα and the NF-κB p65 subunit during this process suggests a potential link between adipogenic signaling, inflammation, and MPTP gain-of-function, thus altering BMSC fate during aging.
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http://dx.doi.org/10.1016/j.jbc.2023.105458 | DOI Listing |
ACS Omega
December 2024
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Targeting nonapoptotic cell death offers a promising strategy for overcoming apoptosis resistance in cancer. In this study, we developed Tat-Ram13, a 25-mer peptide that fuses the NOTCH1 intracellular domain fragment RAM13 with a cell-penetrating HIV-1 TAT, for the treatment of T-cell acute lymphoblastic leukemia with aberrant NOTCH1 mutation. Tat-Ram13 significantly downregulated NOTCH1-target genes in T-ALL cell lines.
View Article and Find Full Text PDFBiomed Pharmacother
December 2024
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, Republic of Korea; School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address:
mPTP is a multi-protein complex that opens in mitochondria during cell death. Cisplatin-induced hearing loss is also known to be caused by mPTP opening. Thus, our study evaluated the protective effect of a novel mPTP inhibitor named DBP-iPT against cisplatin-induced hearing loss.
View Article and Find Full Text PDFJ Anim Sci
December 2024
Key Laboratory for Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Bacterial contamination is an inevitable issue during the processing of semen preservation in pigs. As a prototypical endotoxin from Gram-negative bacteria in semen, lipopolysaccharide (LPS) undermines sperm function during liquid preservation. Spermine and spermidine could protect cells against LPS-induced injury, and the content of spermine and spermidine in seminal plasma is positively correlated with sperm quality.
View Article and Find Full Text PDFToxicol In Vitro
December 2024
Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez, Avenida Dr. Márquez 162, Colonia Doctores, Cuauhtémoc, 06720 Ciudad de México, Mexico. Electronic address:
Benzo[ghi] perylene (b[ghi]p) is classified as non-carcinogenic to humans, and there are currently no occupational exposure models available to identify its effects. The aim of this work was to evaluate the effect of b[ghi]p on the lysosomes of NL-20 cells (a human bronchial cell line) exposed to 4.5 μM for 3 h.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address:
Hexokinase 2 (HK2) plays a vital role in mitochondrial homeostasis; however, the molecular mechanisms underlying its involvement in high-concentrate diet-induced damage in the ruminal epithelium of dairy cows are poorly understood. This study aimed to explore the regulatory role of HK2 in mitochondrial function and responses to inflammation in the rumen of dairy cows fed a high-concentrate diet. Our results showed that, compared with a low-concentrate (LC) diet, feeding a high-concentrate (HC) diet increased oxidative stress and reduced relative antioxidant gene expression levels and enzyme activities in the ruminal epithelium.
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