SNP-induced apoptosis may be mediated with caspase inhibitor by JNK signaling pathways in rabbit articular chondrocytes

Chen, Qun; Kao, Xibin; Chen, JingHong; Xue, Wanli; Xiong, Yongmin; Wang, ZhiLun

doi:10.2131/jts.37.157

Cited by 22 publications

(13 citation statements)

References 35 publications

(36 reference statements)

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“…It has been reported that the activation of PI3-kinase (PI3K)/Akt and c-jnu N-terminal kinase (JNK)/c-jun pathways regulates cell proliferation and apoptosis in response to various stimuli (14). Therefore, PI3K/Akt and JNK/c-jun kinase pathways were examined to determine if apoptotic effect of WFA is dependent on the PI3K/Akt and JNK/c-jun pathways.…”

Section: Resultsmentioning

confidence: 99%

Withaferin A-Caused Production of Intracellular Reactive Oxygen Species Modulates Apoptosis via PI3K/Akt and JNKinase in Rabbit Articular Chondrocytes

Kim

2014

J Korean Med Sci

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Withaferin A (WFA) is known as a constituent of Ayurvedic medicinal plant, Withania somnifera, and has been used for thousands of years. Although WFA has been used for the treatment of osteoarthritis (OA) and has a wide range of biochemical and pharmacologic activities, there are no findings suggesting its properties on chondrocytes or cartilage. The aim of the present study is to investigate the effects of WFA on apoptosis with focus on generation of intracellular reactive oxygen species (ROS). Here we showed that WFA significantly increased the generation of intracellular ROS in a dose-dependent manner. We also determined that WFA markedly leads to apoptosis as evidenced by accumulation of p53 by Western blot analysis. N-Acetyl-L-Cystein (NAC), an antioxidant, prevented WFA-caused expression of p53 and inhibited apoptosis of chondrocytes. We also found that WFA causes the activation of PI3K/Akt and JNKinase. Inhibition of PI3K/Akt and JNKinase with LY294002 (LY)/triciribine (TB) or SP600125 (SP) in WFA-treated cells reduced accumulation of p53 and inhibited fragmented DNA. Our findings suggested that apoptosis caused by WFA-induced intracellular ROS generation is regulated through PI3K/Akt and JNKinase in rabbit articular chondrocytes.Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Withaferin A-Caused Production of Intracellular Reactive Oxygen Species Modulates Apoptosis via PI3K/Akt and JNKinase in Rabbit Articular Chondrocytes

Kim

2014

J Korean Med Sci

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“…Among the MAPK family, JNK and p38 have been suggested to be apoptosis-inducing pathways complicated in NO toxicity [26,27]. Chen et al reported that pathologically blocking JNK activation could reduce NOinduced apoptosis, indicating an important role of JNK in NO-induced apoptosis [27]. In this report, LPS treatment was followed by rapid JNK phosphorylation and a reduction in Bcl-2 expression and increased Bax expression, contributing to cell apoptosis.…”

Section: Discussionmentioning

confidence: 57%

“…Activated JNK can inactivate its downstream Bcl-2 families, causing the release of cytochrome c, initiating cell death signaling pathways [25]. Among the MAPK family, JNK and p38 have been suggested to be apoptosis-inducing pathways complicated in NO toxicity [26,27]. Chen et al reported that pathologically blocking JNK activation could reduce NOinduced apoptosis, indicating an important role of JNK in NO-induced apoptosis [27].…”

Section: Discussionmentioning

confidence: 99%

Effects of Ghrelin on iNOS-Derived NO Promoted LPS-Induced Pulmonary Alveolar Epithelial A549 Cells Apoptosis

Zeng

Huang

Zheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the process of abnormal apoptosis of pulmonary alveolar type II epithelial A549 cells in acute respiratory distress syndrome (ARDS), inducible nitric oxide synthase (iNOS) activity in the lung, nitric oxide (NO) production, and the level of protein S-nitrosylation were increased. However, the role of excessive NO production in sepsis-induced ARDS is controversial. Additionally, ghrelin is a growth hormone that exerts an inhibitory role in cell apoptosis. We examined the effect of NO and S-nitrosylation on apoptosis of A549 cells induced by Lipopolysaccharide (LPS) and molecular mechanism underlying the anti-apoptotic effect of ghrelin in this process. Methods: Flow cytometry and qPCR were used to detect lentiviral infection efficiency and iNOS gene level, respectively. Extracellular and intracellular NO levels were observed by Griess assay kit and DAF-FM DA. Mitochondrial transmembrane potential, apoptosis rate and SNO levels were determined by flow cytometry, Biotin-Switch method and immunofluoresence staining. The expression of iNOS, apoptotic proteins and JNK were assessed by immunoblot analysis. Results: The results showed about two times increase in iNOS expression and intracellular NO levels response to LPS exposure at 24 hours (P< 0.05), while not in extracellular NO levels. NO donors, S-nitroso-N-acetylpenicillamine (SNAP) significantly raised (36.7%, P< 0.05; 38.4%, P< 0.05; 41.8%, P< 0.05) extracellular NO levels without influencing the intracellular NO levels. LPS increased the apoptosis rate (42.4%±2.6% vs 2.8%±1%, P< 0.05) of A549 accompanied by increased Bax levels and decreased Bcl-2 levels through activating JNK signaling, which was reversed when we diminished the iNOS expression in A549 cells using lentiviral vectors encoding iNOS shRNA in the presence of LPS (24.8%±3.8% vs 42.4%±2.6%, P< 0.05). However, the apoptosis rate was increased when SNAP was added (38.8%±1.3% vs 24.8%±3.8%, P< 0.05). Furthermore, we investigated whether ghrelin exert a protective role against LPS-induced apoptosis and the potential mechanism involved in. Ghrelin alone appeared to decrease iNOS expression (32.3%, P< 0.05; 42.3%, P< 0.05), which showed no signifiant difference between LPS+ghrelin group and LPS group. However, this study showed that ghrelin decreased the intracellular NO production (38.9%, P< 0.05), protein S-nitrosylation levels (33.5%, P< 0.05), Bax protein expression (70.2%, P< 0.05), whereas increasing Bcl-2 protein expression (14.1%, P< 0.05) and mitochondrial transmembrane potential (∆ΨM) (20.7%, P< 0.05) in the presence of LPS. Conclusion: The data suggested that NO derived from iNOS induced by LPS stimulation exerts an important role in promoting apoptosis of A549 cells, and ghrelin abolished intracellular NO production and protein S-nitrosylation levels, abrogating the apoptosis of A549 cells partly through inhibiting mitochondrial-dependent pathways.

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“…Stress‐activated protein kinase/c‐Jun NH 2 ‐terminal kinase (JNK) is significantly involved not only in apoptotic death but also in other forms of cell death, including necrosis and autophagy (Adhami et al, ; Weston and Davis, ). Treatment with exogenous NO by treatment with SNP activates JNK, ERK, and p38 MAP kinase (Chae et al, ; Chae et al, ; Chen et al, ), but activation of the critical kinase that may be involved in SNP‐induced cell death is mediated by the activation of JNK because the dominant‐negative form of JNK strongly suppresses SNP‐induced cell death (Chae et al, ; Chae et al, ). Seeking mechanistic insight into the protective effect of NX‐5, activation of JNK by SNP‐induced phosphorylation at 12 h and 18 h using immunoblotting was investigated.…”

Section: Resultsmentioning

confidence: 99%

NecroX‐5 suppresses sodium nitroprusside‐induced cardiac cell death through inhibition of JNK and caspase‐3 activation

Lee

Kim³

et al. 2014

Cell Biology International

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Although sodium nitroprusside (SNP) is an effective hypotensive drug and is often used in pediatric intensive care units and to treat acute heart failure, clinical application of SNP is limited by its cardiotoxicity. NecroX-5 (NX-5) was recently developed and has the capacity to inhibit necrotic cell death. No current literature addresses whether NX-5 suppresses SNP-induced cell death or its mechanism of action. We have investigated the protective role of NX-5 against SNP-induced cell death in cardiomyocyte-like H9c2 cells. SNP treatment induced severe cell death, possibly through phosphorylation of stress-activated protein kinase/c-Jun NH₂-terminal kinase (JNK) and activation of the apoptotic signaling pathway, including downregulation of Bcl-2 and cleavage of caspase-3. However, NX-5 suppresses SNP-induced cell death through inhibition of JNK activation and suppression of both downregulation of Bcl-2 protein expression and caspase-3 cleavage. These findings will provide insights and facilitate development of antidotes to SNP toxicity in cardiac cells.

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SNP-induced apoptosis may be mediated with caspase inhibitor by JNK signaling pathways in rabbit articular chondrocytes

Cited by 22 publications

References 35 publications

Withaferin A-Caused Production of Intracellular Reactive Oxygen Species Modulates Apoptosis via PI3K/Akt and JNKinase in Rabbit Articular Chondrocytes

Withaferin A-Caused Production of Intracellular Reactive Oxygen Species Modulates Apoptosis via PI3K/Akt and JNKinase in Rabbit Articular Chondrocytes

Effects of Ghrelin on iNOS-Derived NO Promoted LPS-Induced Pulmonary Alveolar Epithelial A549 Cells Apoptosis

NecroX‐5 suppresses sodium nitroprusside‐induced cardiac cell death through inhibition of JNK and caspase‐3 activation

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