High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells
Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/3765173 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832568194572746752 |
|---|---|
| author | Xiaofei Cheng Bin Ni Feng Zhang Ying Hu Jie Zhao |
| author_facet | Xiaofei Cheng Bin Ni Feng Zhang Ying Hu Jie Zhao |
| author_sort | Xiaofei Cheng |
| collection | DOAJ |
| description | Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism. |
| format | Article |
| id | doaj-art-0799b689edce46e88d25f4d68fd5ab2d |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-0799b689edce46e88d25f4d68fd5ab2d2025-02-03T00:59:32ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/37651733765173High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus CellsXiaofei Cheng0Bin Ni1Feng Zhang2Ying Hu3Jie Zhao4Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, ChinaDepartment of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, ChinaDepartment of Toxicity Evaluation, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, ChinaObjectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.http://dx.doi.org/10.1155/2016/3765173 |
| spellingShingle | Xiaofei Cheng Bin Ni Feng Zhang Ying Hu Jie Zhao High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells Journal of Diabetes Research |
| title | High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells |
| title_full | High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells |
| title_fullStr | High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells |
| title_full_unstemmed | High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells |
| title_short | High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells |
| title_sort | high glucose induced oxidative stress mediates apoptosis and extracellular matrix metabolic imbalances possibly via p38 mapk activation in rat nucleus pulposus cells |
| url | http://dx.doi.org/10.1155/2016/3765173 |
| work_keys_str_mv | AT xiaofeicheng highglucoseinducedoxidativestressmediatesapoptosisandextracellularmatrixmetabolicimbalancespossiblyviap38mapkactivationinratnucleuspulposuscells AT binni highglucoseinducedoxidativestressmediatesapoptosisandextracellularmatrixmetabolicimbalancespossiblyviap38mapkactivationinratnucleuspulposuscells AT fengzhang highglucoseinducedoxidativestressmediatesapoptosisandextracellularmatrixmetabolicimbalancespossiblyviap38mapkactivationinratnucleuspulposuscells AT yinghu highglucoseinducedoxidativestressmediatesapoptosisandextracellularmatrixmetabolicimbalancespossiblyviap38mapkactivationinratnucleuspulposuscells AT jiezhao highglucoseinducedoxidativestressmediatesapoptosisandextracellularmatrixmetabolicimbalancespossiblyviap38mapkactivationinratnucleuspulposuscells |