Coenzyme Q10 Inhibits the Activation of Pancreatic Stellate Cells through PI3K/AKT/MTOR Signaling Pathway
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// Ran Xue 1 , Jing Yang 2 , Jing Wu 2 , Qinghua Meng 2 and Jianyu Hao 1 1 Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China 2 Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China Correspondence to: Jianyu Hao, email: hao_jianyu@126.com Keywords: pancreatic stellate cell, activation, coenzyme Q10, autophagy, reactive oxygen species Received: May 25, 2017 Accepted: August 07, 2017 Published: September 23, 2017 ABSTRACT Aim: Pancreatic stellate cells (PSCs) have a vital role in pancreatic fibrosis accompanied by pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Any agents which can affect the activation of PSCs could become potential candidates for treatment strategies in PDAC and CP. Our aim was to explore the effect of Coenzyme Q10 (CoQ10) in the process of PSCs activation. Methods: Isolated PSCs from C57BL/6 mice were treated with various dosages of CoQ10 (1, 10, and 100μM) and different time (24h, 48h, and 72 h). Effect of CoQ10 on autophagy, apoptosis, senescence and oxidative stress, as well as the activation of PSCs were analyzed by immunocytofluorescent staining, quantitative real time RT-PCR, western blotting, SA-β-galactosidase staining, malondialdehyde and reactive oxygen species (ROS) assay. Results: Expression of α-smooth muscle actin, LC3II, Beclin1, Cleaved caspases-3 and Bax levels were significantly reduced in CoQ10 treatment groups. Meanwhile, compared with the control group, significant differences for the expression of desmin, P62, Bcl-2, p-PI3K, p-AKT and p-mTOR levels in CoQ10 treatment groups were found. Moreover, CoQ10 affected the secretion of extracellular matrix components for PSCs. Few SA-β-gal positive cells were found in CoQ10 treated groups. A significant decrease in ROS positive cells and malondialdehyde levels were observed after 72 h exposure to CoQ10. Conclusions: Our finding suggests that CoQ10 inhibits the activation of PSCs by suppressing autophagy through activating the PI3K/AKT/mTOR signaling pathway. CoQ10 may act as a therapeutic agent in PSC-relating pathologies and/or anti-fibrotic approaches.
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Similar beneficial effects of CoQ10 have been obtained in cancer and Alzheimer's disease, in whose pathogenesis OS plays a predominant role.
“Similar beneficial effects have been obtained in cancer and Alzheimer’s disease (AD), in whose pathogenesis OS plays a predominant role [60,61].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [61]
Coenzyme Q10, SkQ1, mitoquinone and methylene blue are among mitochondria targeted antioxidants exerting a role in counteracting OS-induced senescence, with CoQ10 being the most studied.
“Coenzyme Q10 (CoQ10), SkQ1 (a.k.a. visomitin), mitoquinone (MitoQ) and methylene blue are among the mitochondria targeted antioxidants exerting a role in counteracting OS-induced senescence, with CoQ10 being the most studied (Table 1 and Table 2) [57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [61]
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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
- Authors
- Xue, R., Yang, J., Wu, J., Meng, Q., & Hao, J.
- Affiliations
- Beijing Chao-Yang Hospital, Capital Medical University (CN)
- Capital Medical University (CN)
- Corresponding author
- Hao, Jianyu
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2017-09-23
- Volume
- 8
- Issue
- 54
- Pages
- 92300-92311
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5696182
- OpenAlex
- W2757509826
- Cited by
- 51
- References
- 39
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 5
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81470888)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- coenzyme Q10, pancreatic stellate cells, stellate cell activation, PI3K/AKT/mTOR pathway, pancreatic fibrosis, autophagy, reactive oxygen species, oxidative stress, apoptosis, cellular senescence, extracellular matrix secretion, pancreatic ductal adenocarcinoma, chronic pancreatitis, alpha-smooth muscle actin, Beclin-1, LC3
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