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Weyman, Crystal M.


Ischemic injury in skeletal muscle caused by hypoxic (low oxygen) conditions occurs in response to vascular and musculoskeletal traumas, diseases and following reconstructive surgeries. Hypoxia induces apoptotic cell death. We have reported that the protein PUMA plays a critical role in the apoptosis of myoblasts in response to culture in differentiation media as well as exposure to DNA damaging chemotherapeutic agents. We have also determined that the transcription factor MyoD, known to control the differentiation process, also plays a role in these apoptotic processes by directly increasing the expression of PUMA mRNA. Herein, we report an increase in PUMA protein and mRNA in response to hypoxic conditions. Specifically, treatment with cobalt chloride to activate hypoxia-inducible factor 1-alpha (HIF-1A), the transcription factor regulating the response to hypoxia, resulted in nearly a six-fold increase in PUMA mRNA after 3 hours. After six hours of treatment, the elevated level of mRNA was only 2 fold that detected in untreated myoblasts. This elevated level of mRNA resulted in a three-fold increase in PUMA protein after 3 hours that returned almost to untreated levels after 6 hours. Future experiments will focus on determining if MyoD contributes to this increase in PUMA expression.

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College of Sciences and Health Professions


Life Sciences | Medicine and Health Sciences | Physical Sciences and Mathematics

Novel regulation of the pro-apoptotic protein PUMA in response to hypoxia