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Published on: March 18, 2014
Transglutaminase-2 is Involved in Cell Apoptosis of Osteosarcoma Cell Line U2OS Under Hypoxia Condition
Wei Wang1, Xiao Li1, Xiang-Zhen Han1
1Department of Orthopedics, Linyi People's Hospital Affiliated to Shandong University, Linyi, 276000, Shandong, People's Republic of China.
Abstract:
Osteosarcoma is the most common type of solid bone cancer, which is the second leading cause of cancer-related death. Hypoxia is an ordinary phenomenon in solid tumor tissues and can induce cell apoptosis but the specific molecular mechanism remains unclear. In this study, we explored the effect and the molecular mechanism of Transglutaminase 2 (TG2) on cell apoptosis in osteosarcoma U2OS cells under hypoxia. We found the enzymatic activity of TG2 is significantly increased and the expression of TG2 is remarkably up-regulated under hypoxia condition. Cell apoptotic rate is markedly increased upon knockdown of TG2 by siRNA under hypoxia. We further investigated the mechanism of cell apoptosis and found Bax protein is significantly increased after depletion of TG2 under hypoxia. Moreover, our data also show that cytochrome C (Cyt C) is significantly increased in cytoplasm and markedly decreased in mitochondria of U2OS cells after depletion of TG2 under hypoxia. Our results suggest that TG2 can inhibit tumor cell apoptosis through down-regulation of Bax and prevention of release Cyt C from mitochondria into cytoplasm.
Insights
Transglutaminase 2 (TG2) inhibits osteosarcoma cell apoptosis under hypoxia by regulating Bax and cytochrome C release. Lowering TG2 levels increases cell death, suggesting TG2 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Osteosarcoma is the most common bone cancer and a leading cause of cancer death.
- Tumor hypoxia is common and influences cancer progression, including apoptosis.
- The precise molecular mechanisms by which hypoxia affects osteosarcoma cell apoptosis are not fully understood.
Purpose of the Study:
- To investigate the role and molecular mechanism of Transglutaminase 2 (TG2) in osteosarcoma cell apoptosis under hypoxic conditions.
- To elucidate how TG2 expression and activity are affected by hypoxia in U2OS cells.
- To determine the downstream targets and pathways involved in TG2-mediated apoptosis regulation.
Main Methods:
- Utilized osteosarcoma U2OS cell line.
- Induced hypoxia to mimic tumor microenvironment.
- Assessed TG2 enzymatic activity and expression levels.
- Employedsilencing RNA (siRNA) to knockdown TG2 expression.
- Quantified cell apoptosis rates.
- Analyzed protein expression levels of Bax and Cytochrome C (Cyt C) in cytoplasm and mitochondria.
Main Results:
- Hypoxia significantly increased TG2 enzymatic activity and expression in U2OS cells.
- Knockdown of TG2 using siRNA markedly increased the apoptotic rate of U2OS cells under hypoxia.
- TG2 depletion led to increased Bax protein levels.
- TG2 depletion resulted in increased Cyt C release into the cytoplasm and decreased levels in mitochondria.
Conclusions:
- TG2 plays a protective role against apoptosis in osteosarcoma cells under hypoxic conditions.
- TG2 inhibits apoptosis by down-regulating Bax expression and preventing the release of Cytochrome C from mitochondria.
- TG2 represents a potential therapeutic target for enhancing osteosarcoma cell death in hypoxic tumors.
