Modulation of oxidized low-density lipoprotein-affected macrophage efferocytosis by mitochondrial calcium uniporter in a murine model

Lu, Na; Zhu, Jun-fan; Lv, He-fan; Zhang, Hai-peng; Wang, Peng-le; Yang, Jing-jing; Wang, Xian-wei

doi:10.1016/j.imlet.2023.09.003

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…(2014) , flow cytometric analyses using ER-Tracker confirmed that H 2 O 2 exposure induced ER stress in C2C12 cells, in parallel with upregulated level of ER stress marker proteins such as p-PERK, GRP78, and CHOP. Although GRP78 is a PERK regulator, which confers drug resistance and has anti-apoptotic functions, the PERK signaling pathway functions in ROS-induced ER stress-induced apoptosis, and CHOP acts as an initiator of ER stress-related apoptosis ( Lu et al ., 2023 ). However, in the presence of morroniside, the upregulation of these proteins was alleviated, clearly demonstrating that blockade of ER stress mediates the suppression of H 2 O 2 -induced oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress

Hwangbo,

Park,

Bang

et al. 2024

Biomol Ther (Seoul)

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Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis , is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H 2 O 2 ) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H 2 O 2 -induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H 2 O 2 -challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H 2 O 2 -induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H 2 O 2 -mediated calcium (Ca 2+ ) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca 2+ -dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca 2+ -mediated ER stress by minimizing oxidative stress, thereby inhibiting H 2 O 2 -induced cytotoxicity in C2C12 myoblasts.

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Section: Discussionmentioning

confidence: 99%

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress

Hwangbo,

Park,

Bang

et al. 2024

Biomol Ther (Seoul)

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“…Interestingly, the abundance of the dominant-negative subunit MCUb is associated with macrophage polarisation during skeletal muscle regeneration, indicating that the composition of the MCU complex influences macrophage phenotypes 107 . This was underscored by Lu et al 108 , who investigated the role of the MCU in atherosclerosis-mediated efferocytosis dysfunction. Using an MCU-specific inhibitor, they were able to attenuate the upregulation of MCU and MCUR1 and the downregulation of MCUb induced by oxidised low-density lipoprotein, which coincided with reduced production of ROS and pro-inflammatory cytokine and improved efferocytosis 108 .…”

Section: Mitochondrial Bioenergeticsmentioning

confidence: 99%

“…This was underscored by Lu et al 108 , who investigated the role of the MCU in atherosclerosis-mediated efferocytosis dysfunction. Using an MCU-specific inhibitor, they were able to attenuate the upregulation of MCU and MCUR1 and the downregulation of MCUb induced by oxidised low-density lipoprotein, which coincided with reduced production of ROS and pro-inflammatory cytokine and improved efferocytosis 108 . In DCs, circadian changes in mitochondrial Ca 2+ have also been found to regulate antigen processing and T cell activation 109 .…”

Section: Mitochondrial Bioenergeticsmentioning

confidence: 99%

Multifaceted mitochondria in innate immunity

Marques,

Kramer,

Ryan

2024

npj Metab Health Dis

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The ability of mitochondria to transform the energy we obtain from food into cell phosphorylation potential has long been appreciated. However, recent decades have seen an evolution in our understanding of mitochondria, highlighting their significance as key signal-transducing organelles with essential roles in immunity that extend beyond their bioenergetic function. Importantly, mitochondria retain bacterial motifs as a remnant of their endosymbiotic origin that are recognised by innate immune cells to trigger inflammation and participate in anti-microbial defence. This review aims to explore how mitochondrial physiology, spanning from oxidative phosphorylation (OxPhos) to signalling of mitochondrial nucleic acids, metabolites, and lipids, influences the effector functions of phagocytes. These myriad effector functions include macrophage polarisation, efferocytosis, anti-bactericidal activity, antigen presentation, immune signalling, and cytokine regulation. Strict regulation of these processes is critical for organismal homeostasis that when disrupted may cause injury or contribute to disease. Thus, the expanding body of literature, which continues to highlight the central role of mitochondria in the innate immune system, may provide insights for the development of the next generation of therapies for inflammatory diseases.

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Hesperidin protects C2C12 myoblasts from oxidative damage by reducing ROS-mediated mitochondrial damage and endoplasmic reticulum stress

Choi

2024

Mol. Cell. Toxicol.

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Modulation of oxidized low-density lipoprotein-affected macrophage efferocytosis by mitochondrial calcium uniporter in a murine model

Cited by 5 publications

References 36 publications

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress

Multifaceted mitochondria in innate immunity

Hesperidin protects C2C12 myoblasts from oxidative damage by reducing ROS-mediated mitochondrial damage and endoplasmic reticulum stress

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