Disequilibrium in the Thioredoxin Reductase-1/Thioredoxin-1 Redox Couple Is Associated with Increased T-Cell Apoptosis in Children with Autism

被引:3
|
作者
Alshehri, Samiyah [1 ]
Nadeem, Ahmed [1 ]
Ahmad, Sheikh F. [1 ]
Alqarni, Sana S. [2 ]
Al-Harbi, Naif O. [1 ]
Al-Ayadhi, Laila Y. [3 ]
Attia, Sabry M. [1 ]
Alqarni, Saleh A. [1 ]
Bakheet, Saleh A. [1 ]
机构
[1] King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh 11451, Saudi Arabia
[2] King Saud Univ, Coll Appl Med Sci, Dept Med Lab Sci, Riyadh 11451, Saudi Arabia
[3] King Saud Univ, Coll Med, Dept Physiol, Riyadh 11451, Saudi Arabia
关键词
ASD; T cells; TrxR1; Trx1; inflammation; immune system; apoptosis; SPECTRUM DISORDERS; OXIDATIVE STRESS; ANTIOXIDANTS; EXPRESSION; SYSTEM; HEALTH;
D O I
10.3390/metabo13020286
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autism spectrum disorder (ASD) is a neuropsychiatric childhood disorder that affects social skill and language development, and is characterized by persistent stereotypic behaviors, restricted social interests, and impaired language/social skills. ASD subjects have dysregulated immune responses due to impairment in inflammatory and antioxidant signaling in immune cells, such as T cells. Thioredoxin reductase-1 (TrxR1) and thioredoxin-1 (Trx1) play a crucial role in the maintenance of redox equilibrium in several immune cells, including T cells. T-cell apoptosis plays a crucial role in the pathogenesis of several inflammatory diseases. However, it remains to be explored how the TrxR1/Trx1 redox couple affects T-cells apoptosis in ASD and typically developing control (TDC) groups. Therefore, this single-center cross-sectional study explored the expression/activity of TrxR1/Trx1, and Bcl2, 7-AAD/annexin V immunostaining in T cells of ASD (n = 25) and TDC (n = 22) groups. Further, effects of the LPS were determined on apoptosis in TDC and ASD T cells. Our data show that T cells have increased TrxR1 expression, while having decreased Trx1 expression in the ASD group. Further, TrxR enzymatic activity was also elevated in T cells of the ASD group. Furthermore, T cells of the ASD group had a decreased Bcl2 expression and an increased % of annexin V immunostaining. Treatment of T cells with LPS caused greater apoptosis in the ASD group than the TDC group, with same treatment. These data reveal that the redox couple TrxR1/Trx1 is dysregulated in T cells of ASD subjects, which is associated with decreased Bcl2 expression and increased apoptosis. This may lead to decreased survival of T cells in ASD subjects during chronic inflammation. Future studies should investigate environmental factors, such as gut dysbiosis and pollutants, that may cause abnormal immune responses in the T cells of ASD subjects due to chronic inflammation.
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页数:12
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