Arachidonic acid impairs the function of the blood-testis barrier via triggering mitochondrial complex-ROS-P38 MAPK axis in hyperthermal Sertoli cells

Bibliographic Details
Title: Arachidonic acid impairs the function of the blood-testis barrier via triggering mitochondrial complex-ROS-P38 MAPK axis in hyperthermal Sertoli cells
Authors: Yu Hu, Han Hu, Ling Yin, Li Wang, KeYan Luo, NanJian Luo
Source: Ecotoxicology and Environmental Safety, Vol 252, Iss , Pp 114598- (2023)
Publisher Information: Elsevier, 2023.
Publication Year: 2023
Collection: LCC:Environmental pollution
LCC:Environmental sciences
Subject Terms: Arachidonic acid, Blood-testis barrier, Mitochondrial, Heat stress, Sertoli cells, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350
More Details: The death of Sertoli cells (SCs) under condition of heat stress (HS) affects spermatogenesis and is associated with impaired function of the blood-testis barrier (BTB). The fatty acid arachidonic acid (AA) is essential for the maintenance of cellular function. However, excessive release of AA during HS may adversely affect the reproductive function. The molecular mechanisms through which AA modulates the BTB in SCs are unclear. In this study, we found that 100 µM AA damaged testicular morphology and accelerated SC apoptosis during HS, reducing the stability of tight junction proteins (TJPs), shown by measurement of the levels of Claudin 11, 5, Occludin, and trans-epithelial electrical resistance (TEER). It was also found that AA adversely affected TJPs by increasing the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), activating p38 mitogen-activated protein kinases (P38 MAPK) and reducing mitochondria DNA (mtDNA) and the expression of mitochondrial complexes I and III. In contrast, pretreatment with SB203508 (a P38 MAPK inhibitor), Rotenone (an inhibitor of complex I) and Antimycin A1 (an inhibitor of complex III) reversed TJPs degradation induced by AA. Interestingly, pretreatment of cells with 10 µM Baicalein, a 12/15 lipoxygenase (12/15-LOX) -dependent inhibitor of AA production, protected against AA-induced TJPs degradation, restored mitochondrial function, and reduced apoptosis. These results suggested an intriguing link between the induction of TJPs degradation induced by AA overload and mitochondrial antioxidant function during HS, which was found to be regulated by the mitochondrial complex-ROS-P38 MAPK axis.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 0147-6513
Relation: http://www.sciencedirect.com/science/article/pii/S0147651323001021; https://doaj.org/toc/0147-6513
DOI: 10.1016/j.ecoenv.2023.114598
Access URL: https://doaj.org/article/b161b87c05274aacb4ffb8f1f19bdbd6
Accession Number: edsdoj.b161b87c05274aacb4ffb8f1f19bdbd6
Database: Directory of Open Access Journals
More Details
ISSN:01476513
DOI:10.1016/j.ecoenv.2023.114598
Published in:Ecotoxicology and Environmental Safety
Language:English