Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

An Erratum to this article was published on 03 October 2017

This article has been updated

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Change history

  • 03 October 2017

    An erratum to this article has been published.

References

  1. Lee, S. H., & Dominguez, R. (2010). Regulation of actin cytoskeleton dynamics in cells. Mol Cells, 29, 311–325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Condeelis, J., Singer, R. H., & Segall, J. E. (2005). The great escape: when cancer cells hijack the genes for chemotaxis and motility. Annu Rev Cell Dev Biol, 21, 695–718.

    Article  CAS  PubMed  Google Scholar 

  3. Doctor, R. B., & Fouassier, L. (2002). Emerging roles of the actin cytoskeleton in cholangiocyte function and disease. Semin Liver Dis, 22, 263–276.

    Article  CAS  PubMed  Google Scholar 

  4. Machesky, L. M., & Insall, R. H. (1998). Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol, 8, 1347–1356.

    Article  CAS  PubMed  Google Scholar 

  5. Myers, K. A., He, Y., Hasaka, T. P., & Baas, P. W. (2006). Microtubule transport in the axon: re-thinking a potential role for the actin cytoskeleton. Neuroscientist, 12, 107–118.

    Article  CAS  PubMed  Google Scholar 

  6. Yamaguchi, H., & Condeelis, J. (2007). Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta, 1773, 642–652.

    Article  CAS  PubMed  Google Scholar 

  7. Yin, H. L., & Stossel, T. P. (1979). Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature, 281, 583–586.

    Article  CAS  PubMed  Google Scholar 

  8. Silacci, P., Mazzolai, L., Gauci, C., Stergiopulos, N., Yin, H. L., & Hayoz, D. (2004). Gelsolin superfamily proteins: key regulators of cellular functions. Cell Mol Life Sci, 61, 2614–2623.

    Article  CAS  PubMed  Google Scholar 

  9. Sun, H. Q., Yamamoto, M., Mejillano, M., & Yin, H. L. (1999). Gelsolin, a multifunctional actin regulatory protein. J Biol Chem, 274, 33179–33182.

    Article  CAS  PubMed  Google Scholar 

  10. Li, G. H., Arora, P. D., Chen, Y., McCulloch, C. A., & Liu, P. (2010). Multifunctional roles of gelsolin in health and diseases. Med Res Rev, 32, 999–1025.

    Article  PubMed  Google Scholar 

  11. Nag, S., Ma, Q., Wang, H., Chumnarnsilpa, S., Lee, W. L., Larsson, M., et al. (2009). Ca2 + binding by domain 2 plays a critical role in the activation and stabilization of gelsolin. Proc Natl Acad Sci USA, 106, 13713–13718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Janmey, P. A., & Stossel, T. P. (1989). Gelsolin-polyphosphoinositide interaction. Full expression of gelsolin-inhibiting function by polyphosphoinositides in vesicular form and inactivation by dilution, aggregation, or masking of the inositol head group. J Biol Chem, 264, 4825–4831.

    CAS  PubMed  Google Scholar 

  13. Meerschaert, K., De Corte, V., De Ville, Y., Vandekerckhove, J., & Gettemans, J. (1998). Gelsolin and functionally similar actin-binding proteins are regulated by lysophosphatidic acid. EMBO J, 17, 5923–5932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee, S. H., Wolf, P. L., Escudero, R., Deutsch, R., Jamieson, S. W., & Thistlethwaite, P. A. (2000). Early expression of angiogenesis factors in acute myocardial ischemia and infarction. Engl J Med, 342, 626–633.

    Article  CAS  Google Scholar 

  15. Hsieh, S. R., Cheng, W. C., Su, Y. M., Chiu, C. H., & Liou, Y. M. (2014). Molecular targets for anti-oxidative protection of green tea polyphenols against myocardial ischemic injury. BioMedicine, 4, 7–16.

    Article  Google Scholar 

  16. Wang, C. H., Lin, W. D., Bau, D. T., Chou, I. C., Tsai, C. H., & Tsai, F. J. (2013). Appearence of acanthosis nigricans may precde obesity: An involvement of the insulin/IGF receptor signaling pathway. BioMedicine, 3, 82–87.

    Article  Google Scholar 

  17. Yang, J., Moravec, C. S., Sussman, M. A., DiPaola, N. R., Fu, D., Hawthorn, L., et al. (2000). Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation, 102, 3046–3052.

    Article  CAS  PubMed  Google Scholar 

  18. Li, G. H., Shi, Y., Chen, Y., Sun, M., Sader, S., Maekawa, Y., et al. (2009). Gelsolin regulates cardiac remodeling after myocardial infarction through DNase I-mediated apoptosis. Circ Res, 104, 896–904.

    Article  CAS  PubMed  Google Scholar 

  19. Nishio, R., & Matsumori, A. (2009). Gelsolin and cardiac myocyte apoptosis: a new target in the treatment of postinfarction remodeling. Circ Res, 104, 829–831.

    Article  CAS  PubMed  Google Scholar 

  20. Mani, S. K., Shiraishi, H., Balasubramanian, S., Yamane, K., Chellaiah, M., Cooper, G., et al. (2008). In vivo administration of calpeptin attenuates calpain activation and cardiomyocyte loss in pressure-overloaded feline myocardium. Am J Physiol Heart Circ Physiol, 295, 314–326.

    Article  Google Scholar 

  21. Mannherz, H. G., Peitsch, M. C., Zanotti, S., Paddenberg, R., & Polzar, B. (1995). A new function for an old enzyme: the role of DNase I in apoptosis. Curr Top Microbiol Immunol, 198, 161–174.

    CAS  PubMed  Google Scholar 

  22. Lazarides, E., & Lindberg, U. (1974). Actin is the naturally occurring inhibitor of deoxyribonuclease I. Proc Natl Acad Sci USA, 71, 4742–4746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chhabra, D., Nosworthy, N. J., & dos Remedios, C. G. (2005). The N-terminal fragment of gelsolin inhibits the interaction of DNase I with isolated actin, but not with the cofilin-actin complex. Proteomics, 5, 3131–3136.

    Article  CAS  PubMed  Google Scholar 

  24. Berk, B. C., Vekshtein, V., Gordon, H. M., & Tsuda, T. (1989). Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells. Hypertension, 13, 305–314.

    Article  CAS  PubMed  Google Scholar 

  25. Geisterfer, A. A., Peach, M. J., & Owens, G. K. (1988). Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res, 62, 749–756.

    Article  CAS  PubMed  Google Scholar 

  26. Chang, Y. M., Velmurugan, B. K., Kuo, W. W., Chen, Y. H., Ho, T. J., Tsai, C. T., et al. (2013). Inhibitory effect of alpinate Oxyphyllae fructus extracts on Ang II-induced cardiac pathological remodeling-related pathways in H9c2 cardiomyoblast cells. BioMedicine, 3, 148–152.

    Article  Google Scholar 

  27. Zou, Y., Komuro, I., Yamazaki, T., Kudoh, S., Uozumi, H., Kadowaki, T., et al. (1999). Both Gs and Gi proteins are critically involved in isoproterenol-induced cardiomyocyte hypertrophy. J Biol Chem, 274, 9760–9770.

    Article  CAS  PubMed  Google Scholar 

  28. Arora, P. D., Glogauer, M., Kapus, A., Kwiatkowski, D. J., & McCulloch, C. A. (2004). Gelsolin mediates collagen phagocytosis through a rac-dependent step. Mol Biol Cell, 15, 588–599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Blaich, A., Pahlavan, S., Tian, Q., Oberhofer, M., Poomvanicha, M., Lenhardt, P., et al. (2012). Mutation of the calmodulin binding motif IQ of the L-type Ca(v)1.2 Ca2+ channel to EQ induces dilated cardiomyopathy and death. J Biol Chem, 287, 22616–22625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mazumdar, B., Meyer, K., & Ray, R. (2012). N-terminal region of gelsolin induces apoptosis of activated hepatic stellate cells by a caspase-dependent mechanism. PLoS One, 7, e44461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

  1. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan

    Yu-Lan Yeh

  2. Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan

    Yu-Lan Yeh

  3. Graduate Institute of Basic Medical Science, School of Chinese Medicine, China Medical University and Hospital, 91 Hsueh-Shih Road 404, Taichung, Taiwan, ROC

    Wei-Jen Ting & Chih-Yang Huang

  4. Department of Nursing, MeiHo University, Pingtung, Taiwan

    Chia-Yao Shen & Cecilia-Hsuan Day

  5. Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan

    Hsi-Hsien Hsu

  6. Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan County, Taiwan

    Li-Chin Chung

  7. Division of Chest Medicine, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan

    Chuan-Chou Tu

  8. Department of Health, Tsao-Tun Psychiatric Center, Executive Yuan, Nantou, 54249, Taiwan

    Sheng-Huang Chang

  9. School of Chinese Medicine, China Medical University, Taichung, Taiwan

    Yuhsin Tsai & Chih-Yang Huang

  10. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

    Chih-Yang Huang

Authors
  1. Yu-Lan Yeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei-Jen Ting
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chia-Yao Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hsi-Hsien Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Chin Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chuan-Chou Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sheng-Huang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cecilia-Hsuan Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuhsin Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chih-Yang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chih-Yang Huang.

Ethics declarations

Conflict of Interests

The authors declare that they have no competing interests.

Additional information

An erratum to this article is available at https://doi.org/10.1007/s12013-017-0819-0.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yeh, YL., Ting, WJ., Shen, CY. et al. Hypoxia Augments Increased HIF-1α and Reduced Survival Protein p-Akt in Gelsolin (GSN)-Dependent Cardiomyoblast Cell Apoptosis. Cell Biochem Biophys 74, 221–228 (2016). https://doi.org/10.1007/s12013-016-0729-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-016-0729-6

Keywords

Search

Navigation