Mitochondrial Transplantation Attenuates Brain Dysfunction in Sepsis by Driving Microglial M2 Polarization

Yan, Chaoying; Ma, Zhi; Ma, Hongli; Li, Qing; Zhai, Qian; Jiang, Tao; Zhang, Zhanqin; Wang, Qiang

doi:10.1007/s12035-020-01994-3

Cited by 44 publications

(24 citation statements)

References 59 publications

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“…Previous research showed that IL-13 could maintain and increase the function and morphology of mitochondria in different diseases. For example, IL-13 could prevent and treat sepsis-induced brain dysfunction by enhancing the mitochondrial function and content in the brain microglia (Yan et al, 2020). In addition, latest research demonstrated that IL-13 mediated the mitochondrial metabolism from glycolysis switch into fatty acid oxidation, thus improving skeletal muscle endurance (Knudsen et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria

Guo

Hong

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Sepsis-induced cardiac injury (SIC) is one of the most common complications in the intensive care unit (ICU) with high morbidity and mortality. Mitochondrial dysfunction is one of the main reasons for SIC, and Interleukin-13 (IL-13) is a master regulator of mitochondria biogenesis. The aim of the present study was to investigate the role of IL-13 in SIC and explore the underlying mechanism. It was found that reactive oxygen species (ROS) production and apoptosis were significantly increased in lipopolysaccharide (LPS)-stimulated primary cardiomyocytes, which was accompanied with obvious mitochondria dysfunction. The results of RNA-sequencing (RNA-seq), mitochondrial membrane potential, fatty acid uptake and oxidation rate suggested that treatment with IL-13 could restore the function and morphology of mitochondria, indicating that it played an important role in protecting septic cardiomyocytes. These findings demonstrated that IL-13 alleviated sepsis-induced cardiac inflammation and apoptosis by improving mitochondrial fatty acid uptake and oxidation, suggesting that IL-13 may prove to be a potential promising target for SIC treatment.

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Section: Discussionmentioning

confidence: 99%

IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria

Guo

Hong

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…A lot of new studies have reported the MT function in the recent two years, while most of them aimed to expand the utility of MT in various biological context, like in diabetic hearts [6], ex-situ-perfused hearts donated after circulatory death [27], acute limb ischemia [10], brain in Sepsis [28], lung injury [5], acute kidney injury [7], aging-related hair loss [29] etc., and even a new clinical study in pediatric patients undergoing cardiogenic shock [13]. However, the mechanisms of MT still kept on being questioned [18,19], especially considering that mitochondria cannot survive under calcium overload during transplantation [20].…”

Section: Discussionmentioning

confidence: 99%

Mitochondria structural integrity is essential for the protection of mitochondrial transplantation against UV-induced cell death

Cao

et al. 2021

Preprint

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Background: Mitochondrial transplantation (MT) is a new technology developed in recent years, which injects healthy mitochondria directly into damaged tissues or blood vessels to play a therapeutic role. It has been studied in many animal models of various diseases, such as myocardial ischemia, cerebral stroke, liver and lung injury, and even has been successfully used in the treatment of childhood heart disease. MT can quickly improve tissue function within a few minutes after injection. This fast response is what is frequently questioned, for it is hard to understand how the whole mitochondria transport to the damaged sites, enter cells and function within such a short period of time. Are there any small molecules of mitochondrial component rather than the whole mitochondria that being responsible for the function of MT? To test this hypothesis, we established a much simple ultra-violet (UV)-irradiated HeLa cell model instead of the more complex animal models.Results: The results of colony formation, sulforhodamine B (SRB), and Hoechst 33342/PI double staining assay strongly indicated that MT exhibited a significant protective effect on UV irradiation damage. The UV irradiation-induced cell cycle arrest at S phase, apoptosis, mitochondrial membrane potential (MMP) decreasing, and the related apoptosis signalling factors p-IKKα, p-p65, I-κB and the activation of caspase3 were all reversed by MT treatments to some extent. Furthermore, mechanisms of MT were evaluated through comparing the effect of thermal inactivation, ultrasonic crushing, and repeated freezing and thawing treatments on MT function. The results denied the above hypothesis that mitochondrial component may function to MT, excluded the function of ATP, mtDNA and other small molecules, and indicated that the mitochondria structural integrity is essential.Conclusions: Our data support a potent anti-UV irradiation effect of MT, and structural integrity of mitochondria is critical for its function.

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“…Classical activation of microglia with LPS/IFN-γ (M1-polarized) decreases mitochondrial content and shifts metabolism from oxidative phosphorylation to glycolysis. Alternatively, activated microglia with IL-4/IL-13 (M2-polarized) resulted in enhanced mitochondrial content and function [ 78 ]. M1 microglia increase glucose uptake, the expression of proteins involved in glycolysis, and produce more lactate, and these processes are modulated by NO [ 74 , 79 ].…”

Section: Microglia Metabolic Adaptationsmentioning

confidence: 99%

Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation

et al. 2021

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Frequently underestimated, encephalopathy or delirium are common neurological manifestations associated with sepsis. Brain dysfunction occurs in up to 80% of cases and is directly associated with increased mortality and long-term neurocognitive consequences. Although the central nervous system (CNS) has been classically viewed as an immune-privileged system, neuroinflammation is emerging as a central mechanism of brain dysfunction in sepsis. Microglial cells are major players in this setting. Here, we aimed to discuss the current knowledge on how the brain is affected by peripheral immune activation in sepsis and the role of microglia in these processes. This review focused on the molecular pathways of microglial activity in sepsis, its regulatory mechanisms, and their interaction with other CNS cells, especially with neuronal cells and circuits.

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Mitochondrial Transplantation Attenuates Brain Dysfunction in Sepsis by Driving Microglial M2 Polarization

Cited by 44 publications

References 59 publications

IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria

IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria

Mitochondria structural integrity is essential for the protection of mitochondrial transplantation against UV-induced cell death

Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation

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