Elevated levels of lipids, in particular saturated fatty acids, are known to be associated with type 2 diabetes (T2D) and to have a negative effect on β-cell function and survival. We bring new evidence indicating that palmitate up-regulates cyclooxygenase-2 (COX-2) expression levels in human islets and in MIN6 β cells, and that it is elevated in islets isolated from T2D donors. Both small interfering specific cyclooxygenase-2 small interfering RNA (siRNA) or the COX-2 inhibitor celecoxib significantly inhibited apoptosis induced by palmitate. Prostaglandin E (PGE), the predominant product of COX-2 enzymatic activity, activates membrane receptors, which are members of the GPCR-family (EP1-EP4). In the present study, elevated expression of the PGE receptor subtype 3 (EP3) receptor was observed in β cells exposed to palmitate and in islets from individuals with T2D. Down-regulation of the pathway using EP3 siRNA or the specific L-798,106 antagonist markedly decreased the levels of palmitate-induced apoptosis. Altogether, our data put forward the COX-2-PGE-EP3 pathway as one of the mediators of palmitate-induced apoptosis in β-cells.-Amior, L., Srivastava, R., Nano, R., Bertuzzi, F., Melloul, D. The role of Cox-2 and prostaglandin E receptor EP3 in pancreatic β-cell death.
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http://dx.doi.org/10.1096/fj.201801823R | DOI Listing |
IUCrJ
March 2025
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093 Warsaw, Poland.
Quantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 and COX-2 isoforms. This study analyzed the electrostatic interaction energies of selected NSAIDs (flurbiprofen, ibuprofen, meloxicam and celecoxib) with the active sites of COX-1 and COX-2, revealing significant differences in binding profiles. Flurbiprofen exhibited the strongest interactions with both COX-1 and COX-2, indicating its potent binding affinity.
View Article and Find Full Text PDFQJM
January 2025
Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center, Beijing, 100091, People's Republic of China.
Gastric cancer (GC) is a significant global health challenge, particularly in high-incidence regions like East Asia. Despite improvements in screening and treatment, the progressive nature of precancerous lesions-such as atrophic gastritis, intestinal metaplasia, and dysplasia-necessitates effective prevention strategies. This review evaluates the role of chemoprevention in GC, focusing on agents designed to target these precancerous lesions.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China.
Ginsenoside Rd (Rd) is a bioactive compound predominantly found in Panax ginseng C.A. Meyer and Panax notoginseng (Burkill) F.
View Article and Find Full Text PDFJ Dent Sci
January 2025
Department of Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Background/purpose: Studies have demonstrated a relation between hypercholesterolemia and development of apical periodontitis (AP), but the underlying mechanism is uncertain. 27-hydroxycholesterol (27HC), produced by cytochrome P450 27A1 (CYP27A1)-catalyzed hydroxylation of cholesterol, is known to possess pro-inflammatory activity. Felodipine is an anti-hypertensive agent able to inhibit CYP27A1.
View Article and Find Full Text PDFMol Cell Endocrinol
January 2025
The Gynecology Department, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:
Research Question: To investigate the underlying mechanisms driving the opposing effects of transforming growth factor-beta 1 (TGFβ1) on the proliferation of control (CESCs) and ectopic (EESCs) endometrial stromal cells.
Design: Cell proliferation assays (CCK-8 and colony formation) were employed to assess the effects of TGFβ1 on CESC and EESC proliferation. An immortalized human endometrial stromal cell line (HESC) was used to elucidate the mechanisms behind cytostatic effect of TGFβ1 and the potential role of cyclooxygenase (COX)-2 in mediating the modulation of TGFβ1 signaling.
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