Mitochondrial dysfunction/NLRP3 inflammasome axis contributes to angiotensin II-induced skeletal muscle wasting via PPAR-γ

Liu, Yuqing; Bi, Xiao; Zhang, Yumei; Wang, Yingdeng; Ding, Wei

doi:10.1038/s41374-019-0355-1

Cited by 35 publications

(28 citation statements)

References 36 publications

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“…The mtROS can act as the second messenger to trigger the activation of inflammasomes after the recognition of PAMPs from microbes or DAMPs [49]. In a research about the muscle wasting, the researchers found that angiotensin II can promote the mtROS production as well as MtD, which further activated NLRP3 inflammasome [50].…”

Section: The Role Of Nlrp3 In Inflammationmentioning

confidence: 99%

NLRP3 Inflammasome and Inflammatory Diseases

Wang

Zhang

Xiao

et al. 2020

Oxidative Medicine and Cellular Longevity

177

142

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Almost all human diseases are strongly associated with inflammation, and a deep understanding of the exact mechanism is helpful for treatment. The NLRP3 inflammasome composed of the NLRP3 protein, procaspase-1, and ASC plays a vital role in regulating inflammation. In this review, NLRP3 regulation and activation, its proinflammatory role in inflammatory diseases, interactions with autophagy, and targeted therapeutic approaches in inflammatory diseases will be summarized.

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Section: The Role Of Nlrp3 In Inflammationmentioning

confidence: 99%

NLRP3 Inflammasome and Inflammatory Diseases

Wang

Zhang

Xiao

et al. 2020

Oxidative Medicine and Cellular Longevity

177

142

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“…While not widely studied in skeletal muscle, Boursereau et al (22) have shown that NLRP3 protein exists in skeletal muscle, and levels are induced through lipopolysaccharide stimulation. A more recent investigation suggests that that angiotensin II increases skeletal muscle NLRP3 in ammasome formation, and these events lead to mitochondrial dysfunction and muscle atrophy (23). It is di cult to interpret the signi cance of our ndings given that the cells were not challenged with pro-in ammatory compounds.…”

Section: Discussionmentioning

confidence: 79%

The Effects of a Theacrine-based Supplement on mRNAs Related to Various Metabolic Processes and Sirtuin Activity in vitro

Mumford

Osburn

Roberts

2020

Preprint

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There is evidence in rodents to suggest theacrine-based supplements modulate tissue sirtuin activity as well as other biological processes associated with aging. Herein, we examined if a theacrine-based supplement (NAD3) altered sirtuin activity in vitro while also affecting markers of mitochondrial biogenesis and the mRNA expression of genes related to various cellular processes in muscle. The murine C2C12 myoblast cell line was used for experimentation. Following 7 days of differentiation, myotubes were treated with 0.45 mg/mL of NAD3 (containing ~ 2 mM theacrine) for 3 and 24 hours (n=6 treatment wells per time point). Control treatments consisted of cellulose-only treatments at the same time points. Relative to CTL-treated cells, NAD3 treatments increased (p<0.05) Sirt1 mRNA levels at 3 hours, as well as global sirtuin activity at 3 and 24 hours. While NAD3 treatments decreased mRNA levels of Nfe2l2 at 3 hours and increased levels at 24 hours relative to CTL-treated cells (a gene involved in mitochondrial biogenesis, p<0.05), citrate synthase activity levels (a surrogate of mitochondrial density) remained unaltered between treatments. NAD3 treatments for 3 and 24 hours decreased Nlrp3 mRNA levels relative to CTL-treated cells (an inflammatory marker, p<0.05). Additionally, NAD3 treatments decreased Map1lc3b mRNA levels (an autophagy marker) after 24-hour treatments (p<0.05). Although these data are limited to select biomarkers in vitro, these preliminary findings suggest a theacrine-based supplement can modulate various skeletal muscle biomarkers related to sirtuin activity, inflammation, and autophagy. Muscle biopsy studies in humans are needed to confirm these current findings.

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“…Ang II normally plays a role in the regulation of the kidneys via retaining sodium and losing potassium, and affects blood flow by stimulating the adrenal cortex [ 46 ]. Ang II expression levels are increased in patients suffering from chronic kidney disease or heart failure who display symptoms of muscle loss and muscle wasting [ 47 , 48 ]. Ang II treatment of C2C12 skeletal muscle myotubes induced a dose-dependent effect on the activation of the NLRP3 inflammasome through activation of its downstream components, i.e., ASC, caspase-1, IL-1β and IL-18 [ 47 ].…”

Section: Nlrp3 Inflammasome In Musclesmentioning

confidence: 99%

“…Ang II expression levels are increased in patients suffering from chronic kidney disease or heart failure who display symptoms of muscle loss and muscle wasting [ 47 , 48 ]. Ang II treatment of C2C12 skeletal muscle myotubes induced a dose-dependent effect on the activation of the NLRP3 inflammasome through activation of its downstream components, i.e., ASC, caspase-1, IL-1β and IL-18 [ 47 ]. In parallel, this treatment inhibited the PI3K/AKT/mTOR signaling pathway and increased the levels of major atrogene markers, atrogin-1, muscle RING-finger protein-1 (MuRF-1) and myostatin.…”

Section: Nlrp3 Inflammasome In Musclesmentioning

confidence: 99%

“…In parallel, this treatment inhibited the PI3K/AKT/mTOR signaling pathway and increased the levels of major atrogene markers, atrogin-1, muscle RING-finger protein-1 (MuRF-1) and myostatin. WT mice treated with Ang II presented a muscle wasting and weight loss phenotype along with decreased muscle performance, which was reverted in the NLRP3-KO mice [ 47 ]. The Ang II-induced NLRP3 inflammasome activation was also described to be mediated through mitochondrial ROS and mitochondrial dysfunction.…”

Section: Nlrp3 Inflammasome In Musclesmentioning

confidence: 99%

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Aberrant NLRP3 Inflammasome Activation Ignites the Fire of Inflammation in Neuromuscular Diseases

Péladeau

Sandhu

2021

IJMS

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Inflammasomes are molecular hubs that are assembled and activated by a host in response to various microbial and non-microbial stimuli and play a pivotal role in maintaining tissue homeostasis. The NLRP3 is a highly promiscuous inflammasome that is activated by a wide variety of sterile triggers, including misfolded protein aggregates, and drives chronic inflammation via caspase-1-mediated proteolytic cleavage and secretion of proinflammatory cytokines, interleukin-1β and interleukin-18. These cytokines further amplify inflammatory responses by activating various signaling cascades, leading to the recruitment of immune cells and overproduction of proinflammatory cytokines and chemokines, resulting in a vicious cycle of chronic inflammation and tissue damage. Neuromuscular diseases are a heterogeneous group of muscle disorders that involve injury or dysfunction of peripheral nerves, neuromuscular junctions and muscles. A growing body of evidence suggests that dysregulation, impairment or aberrant NLRP3 inflammasome signaling leads to the initiation and exacerbation of pathological processes associated with neuromuscular diseases. In this review, we summarize the available knowledge about the NLRP3 inflammasome in neuromuscular diseases that affect the peripheral nervous system and amyotrophic lateral sclerosis, which affects the central nervous system. In addition, we also examine whether therapeutic targeting of the NLRP3 inflammasome components is a viable approach to alleviating the detrimental phenotype of neuromuscular diseases and improving clinical outcomes.

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Mitochondrial dysfunction/NLRP3 inflammasome axis contributes to angiotensin II-induced skeletal muscle wasting via PPAR-γ

Cited by 35 publications

References 36 publications

NLRP3 Inflammasome and Inflammatory Diseases

NLRP3 Inflammasome and Inflammatory Diseases

The Effects of a Theacrine-based Supplement on mRNAs Related to Various Metabolic Processes and Sirtuin Activity in vitro

Aberrant NLRP3 Inflammasome Activation Ignites the Fire of Inflammation in Neuromuscular Diseases

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