Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke
Abstract
Rapamycin has been demonstrated to exhibit neuroprotective functions via the activation of autophagy in a cerebral ischemia model. However, the involvement of mitophagy in this process and its contribution to the protection of mitochondrial function remains unknown. The present study explored the characteristics of mitophagy after cerebral ischemia and the effect of rapamycin on mitochondrial function. Male Sprague-Dawley rats underwent transient middle cerebral artery occlusion (tMCAO). Neurological deficits scores; infarct volumes; mitophagy morphology; and the levels of malondialdehyde (MDA), adenosine triphosphate (ATP) and mitochondrial membrane potentials (Δψm) were examined. The expression of LC3, Beclin-1 and p62 in the mitochondrial fraction combined with transmission electronic microscopy were used to explore mitophagic activity after ischemia. We also blocked autophagosome formation using 3-methyladenine (3-MA) to check the linkage between the mitochondrial protective effect of rapamycin and enhanced mitophagy. We observed that rapamycin significantly enhanced mitophagy, as evidenced by the increase in LC3-II and Beclin-1 expression in the mitochondria and p62 translocation to the mitochondria. Rapamycin reduced infarct volume, improved neurological outcomes and inhibited mitochondrial dysfunction compared with the control animals (p<0.05). However, these protective effects were reversed by 3-methyladenine treatment after rapamycin. The present study indicates that…
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Rapamycin treatment partially improved APOE4 astrocytes' mitochondrial function.
“rapamycin treatment, which was shown to stimulate mitophagy40,41,53, partially improved APOE4 astrocytes’ mitochondrial function.”
From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [41]
Rapamycin promotes autophagosome formation and induces mitophagy by upregulating the parkin/PINK1 pathway.
“rapamycin, which promotes autophagosome formation30, and was shown to induce mitophagy by upregulating the parkin/PINK1 pathway25,40–42.”
From Altered mitochondrial dynamics and function in APOE4-expressing astrocytes (2020) · cites this paper as [41]
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Altered mitochondrial dynamics and function in APOE4-expressing astrocytes
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Self-citation
- Authors
- Li, Q., Zhang, T., Wang, J., Zhang, Z., Zhai, Y., Yang, G.-Y., & Sun, X.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Yang, Guo-Yuan
- Sun, Xiaojiang
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 444
- Issue
- 2
- Pages
- 182-188
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1997801295
- Cited by
- 209
- References
- 6
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 11 · 2023: 23 · 2022: 22 · 2021: 18 · 2020: 25 · 2019: 23 · 2018: 19 · 2017: 16 · 2016: 12 · 2015: 8 · 2014: 3
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science and Technology Commission of Shanghai Municipality (10JC1408100)
- National Natural Science Foundation of China (81070939, 31100783, 31171014)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- rapamycin, mitophagy, mitochondrial dysfunction, cerebral ischemia, ischemic stroke, autophagy, LC3, Beclin-1, p62, 3-methyladenine, middle cerebral artery occlusion, neuroprotection, infarct size, mitochondrial membrane potential, oxidative stress
- MeSH terms
- Beclin-1, Sequestosome-1 Protein, Adenosine Triphosphate, Animals, Autophagy, Brain, Brain Ischemia, Immunohistochemistry, Immunosuppressive Agents, Male, Malondialdehyde, Membrane Proteins, Microtubule-Associated Proteins, Mitochondria, Blotting, Western, Rats, Sprague-Dawley, Sirolimus, Infarction, Middle Cerebral Artery, Stroke, Protein Transport, Microscopy, Electron, Transmission, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Rats, Membrane Potential, Mitochondrial, Mitophagy
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