SP600125 blocks the proteolysis of cytoskeletal proteins in apoptosis induced by gas signaling molecule (NO) via decreasing the activation of caspase-3 in rabbit chondrocytes

被引：5

作者：

Kao, Xi-bin ^{[1
,2
]}

Chen, Qun ^{[3
]}

Gao, Yan ^{[4
]}

Fan, Pin ^{[5
]}

Chen, Jing-hong ^{[3
]}

Wang, Zhi-lun ^{[3
]}

Wang, Yan-qi ^{[2
]}

Chen, Ya-ni ^{[2
]}

Yan, Yong-ping ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Changle Western Rd, Xian 710032, Shaanxi, Peoples R China

[2] Inst Hyg Ordnance Ind, Xian 710065, Shaanxi, Peoples R China

[3] Xi An Jiao Tong Univ, Key Lab Trace Elements & Endem Dis, Natl Hlth & Family Planning Commiss Peoples Rupub, Inst Endem Dis,Hlth Sci Ctr, Xian, Shaanxi, Peoples R China

[4] Inst Hlth Supervis, Beilin Dist, Xian 710003, Shaanxi, Peoples R China

[5] Shaanxi Prov Hosp Tradit Chinese Med, Taiyuan, Shanxi, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2018年 / 824卷

基金：

中国国家自然科学基金;

关键词：

Nitric oxide; Apoptosis; Caspase-3; Cytoskeletal protein; Chondrocytes; OXIDE-INDUCED APOPTOSIS; NITRIC-OXIDE; ARTICULAR CHONDROCYTES; CELL-DEATH; KAPPA-B; C-JUN; EXPRESSION; ACTIN; CARTILAGE; PATHWAY;

D O I：

10.1016/j.ejphar.2018.01.032

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

NO plays a key role in the pathological mechanisms of articular diseases. As cytoskeletal proteins are responsible for the polymerization, stabilization, and dynamics of the cytoskeleton network, we investigated whether cytoskeletal proteins are the intracellular pathological targets of NO. We aimed at clarifying whether the cytoskeleton perturbations involved in apoptosis are induced in rabbit articular chondrocytes by NO, which can be liberated by sodium nitroprusside (SNP) treatment. The first passage rabbit articular chondrocytes were cultured as monolayer for the experiments, and the effects of NO were tested in the presence of JNK-specific inhibitor, SP600125. SNP treatment of cultured chondrocytes caused significant apoptosis in a concentration-dependent manner (time and dose), as evaluated by TUNEL assay and Annexin V flow cytometry, while the apoptosis was reduced by the SP600125 addition 30 min before SNP treatment. Besides, SP600125 decreased significantly the protein expression of total caspase-3 and the intracellular gene expression of caspase-3, measured by Western blot analysis and PCR. SP600125 also increased the cytoskeletal protein expressions. These results suggested that JNK pathway plays a critical role in the NO-induced chondrocyte apoptosis, and SP600125 treatment blocks the dissolution of the cytoskeletal proteins via activation of caspase-3 pathways.

引用

页码：40 / 47

页数：8