Background: Papillary cells adapt to their hyperosmotic environment by accumulating organic osmolytes and by enhanced synthesis of heat shock protein 70 (HSP70), which protect against high-solute concentrations. Because cyclooxygenase-2 (COX-2) is expressed abundantly in the renal papilla and is induced by dehydration, and because HSP70 expression is stimulated by specific prostaglandins, COX-2 inhibition may interfere with cellular osmoadaptation.
Methods: In vivo, rats received rofecoxib before water deprivation. Medullary expression of several tonicity-responsive genes was analyzed and apoptosis was monitored by transferase-mediated dUTP nick-end labeled (TUNEL) staining and determination of papillary caspase-3 activity. In vitro, inner medullary collecting duct 3 (IMCD3) cells were exposed to hypertonic medium containing a COX-2-specific inhibitor. Thereafter, expression of tonicity-responsive genes was analyzed and resistance to high-solute concentrations was examined. Further, the effect of Delta 12-PGJ2, a urinary prostaglandin, and of HSP70 overexpression on resistance against high urea concentration, was evaluated.
Results: Rofecoxib treatment significantly increased urine osmolality due to higher urea concentrations, but reduced papillary HSP70 abundance by 50%. TUNEL staining showed numerous apoptotic cells in the papilla, associated with increased caspase-3 activity. These in vivo results were confirmed by experiments on cultured IMCD3 cells, in which COX-2 inhibition impaired the tonicity-induced up-regulation of HSP70 expression and rendered the cells susceptible to high urea concentrations. Furthermore, Delta 12-PGJ2 increased both HSP70 expression and resistance against high urea, which was causally linked to higher HSP70 levels.
Conclusion: These observations support the view that chronic COX-2 inhibition reduces medullary HSP70 expression, thus rendering papillary cells susceptible to damage by high urea concentrations, especially when accompanied by dehydration.
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http://dx.doi.org/10.1111/j.1523-1755.2004.00387.x | DOI Listing |
Drug Des Devel Ther
January 2025
Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
Objective: Neuronal damage is criminal to cognitive dysfunction, closely related to endoplasmic reticulum stress (ERS). However, due to the pathogenesis of endotoxin-induced long-term cognitive dysfunction is not fully clarified, there is still a lack of effective treatment. This study was conducted to explore the protective effects and mechanism of rosmarinic acid (RA) against ERS in endotoxin-induced cognitive dysfunction in mice and neuronal injury in cells.
View Article and Find Full Text PDFClin Exp Emerg Med
January 2025
Department of Emergency Medicine, Chungbuk National University Hospital, 776, Sunhwan-ro, Seowon-gu, Cheongju, Republic of Korea.
Objective: The study aims to investigate the long-term impacts of traumatic brain injury (TBI) on neuroinflammation and neuronal apoptosis in pediatric and adult mice, specifically focusing on how age-at-injury influences these processes.
Methods: Controlled cortical impact (CCI) was used to induce TBI in pediatric (21-25 days old) and adult (8-12 weeks old) C57Bl/6 male mice. Neuroinflammation was evaluated through immunoreactivity for Iba-1 and GFAP, while apoptosis was assessed using markers such as Bax, Bcl- 2, and pro-caspase-3.
Aquat Toxicol
January 2025
Nantes Université, Institut des Substances et Organismes de la Mer, ISOMer, UR 2160, Nantes F-44000, France.
Improving the understanding of how chemicals affect on organisms and assessing the associated environmental risks is of major interest in environmental studies. This can be achieved by using complementary approaches based on the study of the molecular responses of organisms. Because of the known chemical pressures on the environment, regulations on the content of some chemicals, such as cadmium, have been mostly completed.
View Article and Find Full Text PDFPoult Sci
January 2025
Feedworks Pty Ltd, Romsey, VIC, Australia.
The effectiveness of guanidinoacetic acid (GAA) in reduced protein (RP) diets on performance and gut health of broilers under heat stress is largely unknown. A 35-d experiment was conducted using four dietary treatments: a standard protein diet (SP, 22.1 and 20.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
Purpose: To investigate potential modes of programmed cell death in the lens epithelial cells (LECs) of patients with early age-related cortical cataract (ARCC) and to explore early-stage intervention strategies.
Methods: Anterior lens capsules were collected from early ARCC patients for comprehensive analysis. Ultrastructural examination of LECs was performed using transmission electron microscopy.
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