Chlorogenic acid suppresses mitochondrial apoptotic effectors Bax/Bak to counteract Nod-like receptor pyrin domain 3 (NLRP3) inflammasome in thiram exposed chondrocytes

被引：19

作者：

Kulyar, Muhammad Fakhar-E-Alam ^{[1
]}

Yao, Wangyuan ^{[1
]}

Ding, Yanmei ^{[1
]}

Du, Haitao ^{[1
]}

Mo, Quan ^{[1
]}

Pan, Huachun ^{[1
]}

Shahzad, Muhammad ^{[2
]}

Mehmood, Khalid ^{[2
]}

Iqbal, Mudassar ^{[1
,2
]}

Akhtar, Muhammad ^{[1
]}

Waqas, Muhammad ^{[3
]}

Li, Jiakui ^{[1
]}

机构：

[1] Huazhong Agr Univ, Coll Vet Med, Wuhan 430070, Peoples R China

[2] Islamia Univ Bahawalpur, Fac Vet & Anim Sci, Bahawalpur 63100, Pakistan

[3] Univ Poonch, Fac Vet & Anim Sci, Rawalakot 12350, Azad Jammu & Ka, Pakistan

来源：

PHYTOMEDICINE | 2022年 / 95卷

基金：

中国国家自然科学基金;

关键词：

Toxicity; Thiram; Apoptosis; Inflammasome; NLRP3; Tibial dyschondroplasia; NF-KAPPA-B; CELL-DEATH; MEDIATED APOPTOSIS; IN-VIVO; ACTIVATION; CASPASES; PERMEABILIZATION; INHIBITION; INDUCTION; DISEASE;

D O I：

10.1016/j.phymed.2021.153865

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Background: Tibial dyschondroplasia (TD) is a common disease characterized by proliferation and the deterioration of growth plate's chondrocytes due to widespread utilization of thiram in the agriculture and industrial sector. Purpose: In recent years, Nod-like receptor pyrin domain 3 (NLRP3) inflammasome has become a dilemma in the occurrence of many diseases. According to many research investigations, NLRP3 inflammasome has been linked to various diseases caused by pesticides and environmental toxins. Its involvement in such conditions opens up new treatment approaches. However, the role of the NLRP3 inflammasome in the development of TD is not fully understood under the impact of chlorogenic acid (CGA). Methods: Chondrocytes were cultured with our previously developed methodology from growth plates. After morphological and molecular identification, chondrocytes were split into different groups to investigate the efficacy of chlorogenic acid. Cell apoptosis was determined through flow cytometry and Tunnel assay. Furthermore, RT-qPCR, immunofluorescence, and western blotting techniques were used to check marker genes and proteins expression. Results: In thiram-induced TD, Bax/Bak activation persuade a parallel pathway, mediated by the NLRP3 base inflammasome. It is worth mentioning that the apoptotic executioners (caspase-3 and caspase-7) act upstream for inflammasome. Furthermore, chondrocytes' ability to undergo mitochondrial apoptosis was governed by antiapoptotic members, e.g., Bcl-2 and Bcl-xl. Equilibrium of these anti-apoptotic proteins ensured appropriate regulation of apoptosis during the development and survival of chondrocytes. Conclusion: Chondrocytes have ability to undergo Bax/Bak-mediated apoptosis and generate pro-inflammatory signals, e.g., NLRP3 in thiram-induced TD. So, the Nod-like receptor pyrin domain 3 is the potential target to eliminate TD at all stages of pathology, while drugs, e.g., CGA, can significantly improve chondrocytes' survival by targeting these pro-inflammatory signals.

引用

页数：13

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