Role of selenoprotein S (SEPS1) -105G>A polymorphisms and PI3K/Akt signaling pathway in Kashin-Beck disease.

Abstract

OBJECTIVE:

To investigate the relationship between SEPS1 polymorphism and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in Kashin-Beck disease (KBD) and further explore the pathogenesis of KBD.

METHODS:

Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect SEPS1 -105G>A polymorphism in 232 cases and 331 controls. The protein expressions of PI3K/Akt signaling molecules in whole blood and chondrocytes were detected by Western blot.

RESULTS:

The frequencies of SEPS1 -105G>A genotype AA (21.1% vs 3.0%) and minor allele A (34.1% vs 16.0%) in KBD are significantly higher than those in controls (OR: 8.020, 95% confidence interval (95% CI) 6.341-10.290, P < 0.0001; OR: 2.470, 95% CI 2.001-4.463, P < 0.0001, respectively). SEPS1 AA genotype was an independent risk factor for KBD (adjusted OR: 9.345, 95% CI 4.254-20.529; P < 0.0001). The expression of Gβγ, PI3Kp110, pAkt and pGSK3β in KBD group were higher than that in control group (all P < 0.05). Gβγ, pAkt and pGSK3β protein expression of AA and GA increased than GG (all P < 0.05). Cell apoptosis was increasing and molecule expression of PI3K/Akt signaling pathway were up-regulated in the tert-Butyl hydroperoxide (tBHP)-injured group, the cell apoptosis and expression levels of PI3K/Akt in Na2SeO3 group were decreased.

CONCLUSIONS:

The SEPS1 -105G>A is associated with an increased risk of KBD and influences the expression of PI3K/Akt signaling pathway in KBD patients. Apoptosis induced by tBHP in chondrocyte might be mediated via up-regulation of PI3K/Akt, Na2SeO3 has an effect of anti-apoptosis by down-regulating of PI3K/Akt signaling pathway.

• Authors: X A Du, H M Wang, X X Dai, Y Kou, R P Wu, Q Chen, J L Cao, X Y Mo, Y M Xiong
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 23 Issue 2 Pg. 210-6 (Feb 2015) ISSN: 1522-9653 [Electronic] England
• PMID: 25433273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Membrane Proteins
• SELENOS protein, human
• Selenoproteins
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt

Topics

• Case-Control Studies
• Female
• Humans
• Kashin-Beck Disease (etiology, genetics)
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Phosphatidylinositol 3-Kinase (physiology)
• Polymorphism, Genetic
• Proto-Oncogene Proteins c-akt (physiology)
• Selenoproteins (genetics)
• Signal Transduction