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Cell Biochemistry and Biophysics

, Volume 74, Issue 2, pp 221–228 | Cite as

Hypoxia Augments Increased HIF-1α and Reduced Survival Protein p-Akt in Gelsolin (GSN)-Dependent Cardiomyoblast Cell Apoptosis

  • Yu-Lan Yeh
  • Wei-Jen Ting
  • Chia-Yao Shen
  • Hsi-Hsien Hsu
  • Li-Chin Chung
  • Chuan-Chou Tu
  • Sheng-Huang Chang
  • Cecilia-Hsuan Day
  • Yuhsin Tsai
  • Chih-Yang HuangEmail author
Original Paper

Abstract

Cytoskeleton filaments play an important role in cellular functions such as maintaining cell shape, cell motility, intracellular transport, and cell division. Actin-binding proteins (ABPs) have numerous functions including regulation of actin filament nucleation, elongation, severing, capping, cross linking, and actin monomer sequestration. Gelsolin (GSN) is one of the actin-binding proteins. Gelsolin (GSN) is one of the actin-binding proteins that regulate cell morphology, differentiation, movement, and apoptosis. GSN also regulates cell morphology, differentiation, movement, and apoptosis. In this study, we have used H9c2 cardiomyoblast cell and H9c2-GSN stable clones to understand the roles and mechanisms of GSN overexpression in hypoxia-induced cardiomyoblast cell death. The data show that hypoxia or GSN overexpression induces HIF-1α expression and reduces the expression of survival markers p-Akt and Bcl-2 in H9c2 cardiomyoblast cells. Under hypoxic conditions, GSN overexpression further reduces p-Akt expression and elevates total as well as cleaved GSN levels and HIF-1α levels. In addition, GSN overexpression enhances apoptosis in cardiomyoblasts under hypoxia. Hypoxic challenge further induced activated caspase-3 and cell death that was attenuated after GSN knock down, which implies that GSN is a critical therapeutic target against hypoxia-induced cardiomyoblast cell death.

Keywords

Gelsolin Hypoxia p-Akt HIF-1α Cardiomyoblast cell apoptosis 

Notes

Acknowledgments

This study was supported by China Medical University (CMU102-S-13 and CMUBH R102-008), also in part by the Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH102-TD-B-111-004) and Taiwan Ministry of Health Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-113019).

Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yu-Lan Yeh
    • 1
    • 2
  • Wei-Jen Ting
    • 3
  • Chia-Yao Shen
    • 4
  • Hsi-Hsien Hsu
    • 5
  • Li-Chin Chung
    • 6
  • Chuan-Chou Tu
    • 7
  • Sheng-Huang Chang
    • 8
  • Cecilia-Hsuan Day
    • 4
  • Yuhsin Tsai
    • 9
  • Chih-Yang Huang
    • 3
    • 9
    • 10
    Email author
  1. 1.Department of PathologyChanghua Christian HospitalChanghuaTaiwan
  2. 2.Department of Medical Technology, Jen-Teh Junior College of MedicineNursing and ManagementMiaoliTaiwan
  3. 3.Graduate Institute of Basic Medical Science, School of Chinese MedicineChina Medical University and HospitalTaichungTaiwan, ROC
  4. 4.Department of NursingMeiHo UniversityPingtungTaiwan
  5. 5.Division of Colorectal SurgeryMackay Memorial HospitalTaipeiTaiwan
  6. 6.Department of Hospital and Health Care AdministrationChia Nan University of Pharmacy and ScienceTainan CountyTaiwan
  7. 7.Division of Chest Medicine, Department of Internal MedicineArmed Force Taichung General HospitalTaichungTaiwan
  8. 8.Department of Health, Tsao-Tun Psychiatric CenterExecutive YuanNantouTaiwan
  9. 9.School of Chinese MedicineChina Medical UniversityTaichungTaiwan
  10. 10.Department of Health and Nutrition BiotechnologyAsia UniversityTaichungTaiwan

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