Tags

Type your tag names separated by a space and hit enter

Compression stress induces nucleus pulposus cell autophagy by inhibition of the PI3K/AKT/mTOR pathway and activation of the JNK pathway.
Connect Tissue Res. 2020 Mar 17 [Online ahead of print]CT

Abstract

Purpose:

Reactive oxygen species (ROS) are related to compression stress-induced nucleus pulposus (NP) cell autophagy, but the specific mechanism is unknown in compression stress-induced intervertebral disc degeneration (IVDD). Here, we discuss the specific molecular mechanism and explore whether ROS scavengers could be employed as specific drugs to inhibit compression stress-induced IVDD.

Methods:

Rat NP cells were exposed to 1.0 MPa compression and pretreatment with the ROS scavenger N-acetylcysteine (NAC) or the JNK-selective inhibitor SP600125 not. Intracellular ROS production was monitored by confocal microscopy. Autophagy was detected by observing the NP cell ultrastructural features using TEM and examining autophagic vacuoles by flow cytometry. The levels of autophagy-associated molecules, the JNK pathway and the PI3K/AKT/mTOR pathway were analyzed by western blotting.

Results:

Compression-mediated autophagy in rat NP cells was implicated in ROS generation. The ROS scavenger NAC could protect compression-induced NP cell injures by inhibiting ROS production. And SP600125, a JNK inhibitor, attenuated compression-induced NP cell autophagy. Additionally, this is the first report showing that compression induces autophagy in rat NP cells by impeding the compression-induced ROS dependent PI3K/AKT/mTOR pathway and the ROS independent activation of JNK pathway. And the involvement of JNK pathway was in different mechanism of action that when inhibited leaded to increased cell death, increased generation of ROS but decreased autophagy.

Conclusions:

These results show a new regulatory mechanism involving ROS-mediated autophagy in rat NP cells, which may provide ideas for drug development to improve compression stress-induced IVDD and help avoid eventual surgical treatment of IVD herniation.

Authors+Show Affiliations

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China.Department of Gastroenterology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32180463

Citation

Li, Zhiliang, et al. "Compression Stress Induces Nucleus Pulposus Cell Autophagy By Inhibition of the PI3K/AKT/mTOR Pathway and Activation of the JNK Pathway." Connective Tissue Research, 2020, pp. 1-13.
Li Z, Wang J, Deng X, et al. Compression stress induces nucleus pulposus cell autophagy by inhibition of the PI3K/AKT/mTOR pathway and activation of the JNK pathway. Connect Tissue Res. 2020.
Li, Z., Wang, J., Deng, X., Huang, D., Shao, Z., & Ma, K. (2020). Compression stress induces nucleus pulposus cell autophagy by inhibition of the PI3K/AKT/mTOR pathway and activation of the JNK pathway. Connective Tissue Research, 1-13. https://doi.org/10.1080/03008207.2020.1736578
Li Z, et al. Compression Stress Induces Nucleus Pulposus Cell Autophagy By Inhibition of the PI3K/AKT/mTOR Pathway and Activation of the JNK Pathway. Connect Tissue Res. 2020 Mar 17;1-13. PubMed PMID: 32180463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compression stress induces nucleus pulposus cell autophagy by inhibition of the PI3K/AKT/mTOR pathway and activation of the JNK pathway. AU - Li,Zhiliang, AU - Wang,Jun, AU - Deng,Xiangyu, AU - Huang,Donghua, AU - Shao,Zengwu, AU - Ma,Kaige, Y1 - 2020/03/17/ PY - 2020/3/18/entrez KW - Reactive oxygen species KW - autophagy KW - compression KW - intervertebral disc KW - nucleus pulposus cells SP - 1 EP - 13 JF - Connective tissue research JO - Connect. Tissue Res. N2 - Purpose: Reactive oxygen species (ROS) are related to compression stress-induced nucleus pulposus (NP) cell autophagy, but the specific mechanism is unknown in compression stress-induced intervertebral disc degeneration (IVDD). Here, we discuss the specific molecular mechanism and explore whether ROS scavengers could be employed as specific drugs to inhibit compression stress-induced IVDD.Methods: Rat NP cells were exposed to 1.0 MPa compression and pretreatment with the ROS scavenger N-acetylcysteine (NAC) or the JNK-selective inhibitor SP600125 not. Intracellular ROS production was monitored by confocal microscopy. Autophagy was detected by observing the NP cell ultrastructural features using TEM and examining autophagic vacuoles by flow cytometry. The levels of autophagy-associated molecules, the JNK pathway and the PI3K/AKT/mTOR pathway were analyzed by western blotting.Results: Compression-mediated autophagy in rat NP cells was implicated in ROS generation. The ROS scavenger NAC could protect compression-induced NP cell injures by inhibiting ROS production. And SP600125, a JNK inhibitor, attenuated compression-induced NP cell autophagy. Additionally, this is the first report showing that compression induces autophagy in rat NP cells by impeding the compression-induced ROS dependent PI3K/AKT/mTOR pathway and the ROS independent activation of JNK pathway. And the involvement of JNK pathway was in different mechanism of action that when inhibited leaded to increased cell death, increased generation of ROS but decreased autophagy.Conclusions: These results show a new regulatory mechanism involving ROS-mediated autophagy in rat NP cells, which may provide ideas for drug development to improve compression stress-induced IVDD and help avoid eventual surgical treatment of IVD herniation. SN - 1607-8438 UR - https://www.unboundmedicine.com/medline/citation/32180463/Compression_stress_induces_nucleus_pulposus_cell_autophagy_by_inhibition_of_the_PI3K/AKT/mTOR_pathway_and_activation_of_the_JNK_pathway_ L2 - http://www.tandfonline.com/doi/full/10.1080/03008207.2020.1736578 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.