Cadmium Impairs Autophagy Leading to Apoptosis by Ca2+-Dependent Activation of JNK Signaling Pathway in Neuronal Cells

Xu, Chong; Chen, Sujuan; Xu, Ming; Chen, Xiaoling; Wang, Xiaoxue; Zhang, Hai; Dong, Xiaoqing; Zhang, Ruijie; Chen, Xin; Gao, Wei; Huang, Shile; Chen, Long

doi:10.1007/s11064-021-03341-x

Cited by 13 publications

(23 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, by combining data from our predictive STRING/KEGG and STITCH models ( Figure 2 and Figure 4 ) and our experimental validation experiments ( Figure 3 ), we identified JNK-1/2, p38, JIP-1, and JUN as the main downstream targets responsible for the observed BK channel-mediated inhibition of TNF-α-induced CCL-2 secretion. Since the activation of all four targets (JNK-1/2, p38, JIP-1, JUN) is thought to be a Ca 2+ -dependent process [ 47 , 48 , 49 ], these findings align well with the inhibitory effects of Nifedipine on CCL-2 secretion ( Figure 1 ).…”

Section: Discussionsupporting

confidence: 64%

Activation of Endothelial Large Conductance Potassium Channels Protects against TNF-α-Induced Inflammation

Zyrianova

Zou

López

et al. 2023

IJMS

View full text Add to dashboard Cite

Elevated TNF-α levels in serum and broncho-alveolar lavage fluid of acute lung injury patients correlate with mortality rates. We hypothesized that pharmacological plasma membrane potential (Em) hyperpolarization protects against TNF-α-induced CCL-2 and IL-6 secretion from human pulmonary endothelial cells through inhibition of inflammatory Ca2+-dependent MAPK pathways. Since the role of Ca2+ influx in TNF-α-mediated inflammation remains poorly understood, we explored the role of L-type voltage-gated Ca2+ (CaV) channels in TNF-α-induced CCL-2 and IL-6 secretion from human pulmonary endothelial cells. The CaV channel blocker, Nifedipine, decreased both CCL-2 and IL-6 secretion, suggesting that a fraction of CaV channels is open at the significantly depolarized resting Em of human microvascular pulmonary endothelial cells (−6 ± 1.9 mV), as shown by whole-cell patch-clamp measurements. To further explore the role of CaV channels in cytokine secretion, we demonstrated that the beneficial effects of Nifedipine could also be achieved by Em hyperpolarization via the pharmacological activation of large conductance K+ (BK) channels with NS1619, which elicited a similar decrease in CCL-2 but not IL-6 secretion. Using functional gene enrichment analysis tools, we predicted and validated that known Ca2+-dependent kinases, JNK-1/2 and p38, are the most likely pathways to mediate the decrease in CCL-2 secretion.

show abstract

Section: Discussionsupporting

confidence: 64%

Activation of Endothelial Large Conductance Potassium Channels Protects against TNF-α-Induced Inflammation

Zyrianova

Zou

López

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Extensive investigations have revealed that elevated intercellular Ca 2+ levels induce endoplasmic reticulum stress and constitute a significant proapoptotic signal [40] . In addition, Ca 2+ is also a stimulator of apoptosis and autophagy [41] , [42] . In this study, we explored the anti-osteosarcoma mechanism of baicalin in vitro.…”

Section: Introductionmentioning

confidence: 99%

Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways

Pang

Peng

et al. 2022

Journal of Bone Oncology

View full text Add to dashboard Cite

“…The increased P62 and discontinuous LC3-II may reflect the inhibition of autophagosome degradation [18,45]. In this study, Rotenone-induced apoptosis was observed to be associated with a reduction in the autophagosome of nerve cells (Figure 1, Figure 2-1, and 2-2).…”

Section: Discussionmentioning

confidence: 53%

Ursolic acid inhibits autophagy-dependent neuronal cell death by reducing oxidative stress levels in an in vitro model of Parkinson's disease

Gao

Lei

et al. 2023

Preprint

View full text Add to dashboard Cite

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. The pathogenesis of PD is complicated, resulting from the comprehensive action of many factors [3-5]. In addition, increasing studies have shown that autophagy plays an important role in the development of PD [6-9]. We found that Rotenone caused ROS to build up, which led to apoptosis. However, it is still not clear whether AMPK is involved in Rotenone-induced inhibition of autophagy and apoptosis. We found that Rotenone induced a significant increase in mitochondrial oxidative stress and activated AMPK signaling, leading to a decrease in intracellular autophagy and then apoptosis. The inhibition of autophagy, oxidative stress, and apoptosis induced by Rotenone could be significantly reversed by reducing the oxidative stress level with ursolic acid. In addition, the passivation of AMPK with Ad-dnAMPKα significantly alleviate AMPK phosphorylation, autophagy inhibition, oxidative stress, and apoptosis induced by Rotenone. In conclusion, Rotenone leads to autophagosome-dependent accumulation of apoptosis by inhibiting AMPK-impaired neuronal autophagy flux. Our results highlight that inhibiting AMPK activity and oxidative stress using ursolic acid to improve autophagy levels is a promising strategy to combat Rotenone-induced neurotoxicity.

show abstract

Cadmium Impairs Autophagy Leading to Apoptosis by Ca2+-Dependent Activation of JNK Signaling Pathway in Neuronal Cells

Cited by 13 publications

References 51 publications

Activation of Endothelial Large Conductance Potassium Channels Protects against TNF-α-Induced Inflammation

Activation of Endothelial Large Conductance Potassium Channels Protects against TNF-α-Induced Inflammation

Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways

Ursolic acid inhibits autophagy-dependent neuronal cell death by reducing oxidative stress levels in an in vitro model of Parkinson's disease

Contact Info

Product

Resources

About