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Bone marrow (BM) adipose tissue (BMAT), a unique adipose depot, plays an important role in diseases such as osteoporosis and bone metastasis. Precise control of mesenchymal stem cell (MSC) differentiation is critical for BMAT formation and regeneration. Here, we show that death associated protein kinase 1 (DAPK1) negatively regulates BM adipogenesis in vitro and in vivo. Prx1creDapk1loxp/loxp mice showed more adipocytes in the femur than Dapk1loxp/loxp mice. Further mechanistic analyses revealed that DAPK1 inhibits p38 mitogen-activated protein kinase (MAPK) signaling in the nucleus by binding the p38 isoform MAPK14, decreasing p38 nuclear activity, which subsequently inhibits BM adipogenesis. The inhibitory effect of DAPK1 against MAPK14 was independent of its kinase activity. In addition, the decreased DAPK1 was observed in the BM-MSCs of ageing mice. Our results reveal a previously undescribed function for DAPK1 in the regulation of adipogenesis and may also reveal the underlying mechanism of BMAT formation in ageing.
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http://dx.doi.org/10.1093/stmcls/sxac013 | DOI Listing |
J Biomed Sci
August 2025
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 350401, Taiwan.
Background: The pineal gland produces melatonin to control circadian rhythm via the final enzyme in the serotonin pathway, hydroxyindole O-methyltransferase (HIOMT). Interestingly, HIOMT is expressed by certain non-pineal cells. The main catalytically active of the three human HIOMT (hHIOMT) isoforms in pineal cells is hHIOMT345 (345 amino acids), while hHIOMT298 (298 amino acids) is the most active isoform in fibroblasts, where it converts 5-hydroxytryptophan to 5-methoxytryptophan (5-MTP).
View Article and Find Full Text PDFPhysiol Rep
August 2025
Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
The p38α/β MAPK inhibitor SB203580 in the presence of a phorbol ester (protein kinase C activator) induced cell cycle re-entry of two subpopulations of neonatal rat ventricular cardiomyocytes (NNVMs) distinguished by the absence or de novo nestin expression. Recent studies have reported that the β-adrenergic receptor inhibited the cell cycle re-entry of ventricular cardiomyocytes. The present study tested the hypothesis that sympathetic recruitment of p38α/β MAPK signaling suppressed cell cycle re-entry of one or both subpopulations of 1-day-old NNVMs.
View Article and Find Full Text PDFMol Divers
July 2025
Department of Pharmacognosy, Goa College of Pharmacy, Goa, India.
The p38 mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in inflammatory responses, cell proliferation, differentiation, and cancer progression. Among its four isoforms (p38α, p38β, p38γ, and p38δ), p38α is the most widely studied and has been implicated in various malignancies, making it a compelling target for therapeutic intervention. This review systematically explores recent developments in both synthetic and natural small-molecule inhibitors of p38 MAPK with a focus on their relevance in cancer treatment.
View Article and Find Full Text PDFSci Rep
July 2025
Exercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, School of Physical Therapy, Universidad Andres Bello, Santiago, Chile.
This study aimed to compare the protein content of pathways related to mTORC1 signaling and oxidative metabolism in whole skeletal muscle and isolated muscle fibers from healthy individuals (HEALTHY) and individuals with obesity (OBESE). Muscle biopsies were obtained from 18 individuals. Samples were freeze-dried, and fibers were isolated and fiber-typed for type I and IIa myosin heavy chain isoforms.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
August 2025
Laboratory of Renal Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) contributes to a high rate of morbidity and mortality in many clinical settings. We hypothesized that I/R-induced proximal tubule (PT) injury is associated with inflammation and apoptosis and that PT cell injury may impair Na/H exchanger isoform 3 (NHE3) activity. This study aimed to investigate the relationship between PT injury and NHE3 activity, analyzing the contribution of the p38MAPK/ezrin signaling pathway.
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