Melatonin rescues cerebral ischemic events through upregulated tunneling nanotube-mediated mitochondrial transfer and downregulated mitochondrial oxidative stress in rat brain

Yip, Hon‐Kan; Dubey, Navneet Kumar; Lin, Kun‐Chen; Sung, Pei‐Hsun; Chiang, John Y.; Chu, Yi‐Ching; Huang, Chi‐Ruei; Deng, Yue-Hua; Cheng, Hsin-Chung; Deng, Win-Ping

doi:10.1016/j.biopha.2021.111593

Cited by 29 publications

(19 citation statements)

References 52 publications

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“… Li et al (2021) reported that miR-27A-3p reduces apoptosis and oxidative stress induced by oxygen-glucose deprivation/reoxygenation through FOXO1/p27 Kip1 signaling. Moreover, Yip et al (2021) reported that melatonin reduces apoptotic oxidative stress by repairing impaired metabolic-redox circuits in IS.…”

Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

et al. 2021

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Background: Pharmacological research results showed that total flavonoids of Chuju (TFCJ) could be used to treat acute myocardial ischemia and myocardial ischemia-reperfusion injury. In this study, we explored the protective effect of TFCJ on ischemic stroke (IS) in the IS rat model. We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress that are closely related to PI3K/Akt/mTOR signaling pathway.Method: TFCJ (10, 20, and 40 mg/kg) was administered for 7 days. Rats (260 ± 20 g) were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. The neuroprotective effect of TFCJ was substantiated in terms of neurological deficits, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde), pathomorphological changes (HE staining and TUNEL staining), and neurobehavioral functions in the rats. Then, we employed network pharmacology to reveal the potential mechanism of TFCJ against IS. Western blot was used to determine the levels of PI3K/AKT/mTOR pathway proteins. The expression of BCL-2, BAX, and cleaved-Caspase-3 was also measured by Western blots and RT-PCR.Results: The histopathological assessment showed that TFCJ reduced MCAO-induced brain damage. Besides, TFCJ exerted a protective role in MCAO rats by alleviating cell apoptosis and oxidative stress. Network pharmacology showed that TFCJ might be used against IS through the PI3K/AKT signaling pathway. TFCJ reduced cell apoptosis and oxidative stress by increasing the level of p-AKT and p-mTOR in MCAO rats, while the effect of TFCJ was significantly reversed when applying LY294002 (PI3k inhibitor).Conclusion: These results indicated that TFCJ might decrease oxidative stress and apoptosis that are closely related to PI3K/Akt/mTOR pathway in IS. TFCJ is a promising authentic traditional Chinese medicine for the management of IS.

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Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

et al. 2021

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“…The improved mitochondrial biogenesis and dynamics and the increased donation of mitochondria may support mitochondrial respiration in suffering cells and may foster cell recovery via anastasis 11 . Yip and colleagues published almost simultaneously similar results 101 . These authors using both in vitro and in vivo experimental approaches showed that in the injured area TNTs transfer mitochondria from healthy to apoptotic cells allowing them to recover.…”

Section: Melatonin: a Possible New Role In Mscs Communication?mentioning

confidence: 93%

Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery

Luchetti

Carloni

Nasoni

et al. 2022

Journal of Pineal Research

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Efficient cell-to-cell communication is essential for tissue development, homeostasis, and the maintenance of cellular functions after injury. Tunneling nanotubes (TNTs) have emerged as a new important method of cell-to-cell communication.TNTs are primarily established between stressed and unstressed cells and can transport a variety of cellular components. Mitochondria are important trafficked entities through TNTs. Transcellular mitochondria transfer permits the incorporation of healthy mitochondria into the endogenous network of recipient cells, changing the bioenergetic profile and other functional properties of the recipient and may allow the recipient cells to recuperate from apoptotic processes and return to a normal operating state. Mesenchymal cells (MSCs) can form TNTs and transfer mitochondria and other constituents to target cells. This occurs under both physiological and pathological conditions, leading to changes in cellular energy metabolism and functions. This review summarizes the newly described capacity of melatonin to improve mitochondrial fusion/fission dynamics and promote TNT formation. This new evidence suggests that melatonin's protective effects could be attributed to its ability to prevent mitochondrial damage in injured cells, reduce senescence, and promote anastasis, a natural cell recovery phenomenon that rescues cells from the brink of death. The modulation of these new routes of intercellular communication by melatonin could play a key role in increasing the therapeutic potential of MSCs.

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“…Finally, damaged brain cells, including neurons and astrocytes, were reported to communicate with each other through TNTs. Whether this phenomenon is beneficial or detrimental in the context of ischemic brain repair is not yet known [ 66 , 133 , 134 ].…”

Section: Focus On An Organ: the Brain Role Of Intercellular Communica...mentioning

confidence: 99%

Intercellular Communication in the Brain through Tunneling Nanotubes

Khattar

Safi

Rodriguez

et al. 2022

Cancers

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Intercellular communication is essential for tissue homeostasis and function. Understanding how cells interact with each other is paramount, as crosstalk between cells is often dysregulated in diseases and can contribute to their progression. Cells communicate with each other through several modalities, including paracrine secretion and specialized structures ensuring physical contact between them. Among these intercellular specialized structures, tunneling nanotubes (TNTs) are now recognized as a means of cell-to-cell communication through the exchange of cellular cargo, controlled by a variety of biological triggers, as described here. Intercellular communication is fundamental to brain function. It allows the dialogue between the many cells, including neurons, astrocytes, oligodendrocytes, glial cells, microglia, necessary for the proper development and function of the brain. We highlight here the role of TNTs in connecting these cells, for the physiological functioning of the brain and in pathologies such as stroke, neurodegenerative diseases, and gliomas. Understanding these processes could pave the way for future therapies.

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Melatonin rescues cerebral ischemic events through upregulated tunneling nanotube-mediated mitochondrial transfer and downregulated mitochondrial oxidative stress in rat brain

Cited by 29 publications

References 52 publications

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery

Intercellular Communication in the Brain through Tunneling Nanotubes

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