Human Induced Pluripotent Stem Cells Reveal Mitophagy as an Essential Process Against Diabetic Cardiomyopathy
Abstract/Contents
- Abstract
- Diabetic cardiomyopathy is a common consequence of diabetes and is associated with mitochondrial pathology. Using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as an in vitro model of diabetes, we sought to understand the role of mitophagy, a process that selectively degrades mitochondria through the autophagy-lysosome pathway, as a crucial quality control pathway against diabetic cardiomyopathy. We first showed that iPSC- CMs exposed to a diabetic milieu demonstrated increased hypertrophy, impaired calcium signaling, and higher oxidative stress. Flow cytometry analysis of iPSC- CMs subjected to diabetic conditions revealed two distinct populations of cells (normal and hypertrophied), suggesting a heterogeneous response to hyperglycemia. In these cells, hypertrophied iPSC-CMs were found to have reduced mitophagy compared to normal cells when exposed to hyperglycemia. In addition, we showed that mitochondrial fragmentation was also decreased in the hypertrophied iPSC-CMs compared to normal cells upon exposure to hyperglycemia, demonstrating a link between mitochondrial fragmentation and mitophagy. Surprisingly, pretreatment of iPSC-CMs with a non-selective antioxidant, N-(2-mercaptopropionyl)-glycine, not only failed to limit the deleterious effects of hyperglycemia but actually led to increased hypertrophy and cell death. We found that mitophagy was significantly reduced in iPSC-CMs following antioxidant treatment, suggesting the need for mild oxidative stress as a trigger for mitophagy. Future studies are warranted to further investigate the association between oxidative stress, mitochondrial fragmentation, and mitochondrial fission as targets against diabetic cardiomyopathy.
Description
| Type of resource | text |
|---|---|
| Date created | May 7, 2018 |
Creators/Contributors
| Author | Bae, Michelle Hye Ryeong |
|---|---|
| Degree granting institution | Stanford University, Department of Bioengineering |
| Primary advisor | Wu, Joseph |
| Advisor | Qi, Stanley Lei |
Subjects
| Subject | Stanford School of Engineering |
|---|---|
| Subject | Department of Bioengineering |
| Subject | Stanford Cardiovascular Institute |
| Subject | Undergraduate Advising and Research (UAR) Major Grant |
| Subject | stem cell |
| Subject | diabetes |
| Subject | diabetic cardiomyopathy |
| Subject | cardiology |
| Subject | mitophagy |
| Subject | proteomics |
| Genre | Thesis |
Bibliographic information
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- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Preferred citation
- Preferred Citation
- Bae, Michelle Hye Ryeong. (2018). Human Induced Pluripotent Stem Cells Reveal Mitophagy as an Essential Process Against Diabetic Cardiomyopathy. Stanford Digital Repository. Available at: https://purl.stanford.edu/fv228cg7881
Collection
Undergraduate Theses, School of Engineering
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- Contact
- hbae@stanford.edu
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