Peroxisome Proliferator-activated Receptor-γ Coactivator 1-α (PGC1α) Protects against Experimental Murine Colitis

Cunningham, K.; Vincent, Garret; Sodhi, Chhinder P.; Novak, Elizabeth; Ranganathan, Sarangarajan; Egan, Charlotte E.; Stolz, Donna B.; Rogers, Matthew B.; Firek, Brian; Morowitz, Michael J.; Gittes, George K.; Zuckerbraun, Brian S.; Hackam, David J.; Mollen, Kevin P.

doi:10.1074/jbc.m115.688812

Cited by 75 publications

(97 citation statements)

References 72 publications

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“…As a regulator of mitochondrial biogenesis and function, PGC-1 α plays a remarkable role in resistance to oxidative stress and mitochondrial integrity [47, 48]. There are several studies demonstrating that SIRT1 can enhance PGC-1 α activation and make it act as a substrate of deacetylation [28, 49]. In the present study, we also detected PGC-1 α levels, and its expression was dependent on the concentration of the APN peptide treatments.…”

Section: Discussionsupporting

confidence: 70%

Adiponectin Protects against Glutamate‐Induced Excitotoxicity via Activating SIRT1‐Dependent PGC‐1α Expression in HT22 Hippocampal Neurons

Liang

Zhao

Liu

et al. 2016

Oxidative Medicine and Cellular Longevity

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Glutamate- (Glu-) induced excitotoxicity plays a critical role in stroke. This study aimed to investigate the effects of APN on Glu-induced injury in HT22 neurons. HT22 neurons were treated with Glu in the absence or the presence of an APN peptide. Cell viability was assessed using the MTT assay, while cell apoptosis was evaluated using TUNEL staining. Levels of LDH, MDA, SOD, and GSH-Px were detected using the respective kits, and ROS levels were detected using dichlorofluorescein diacetate. Western blot was used to detect the expression levels of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), cleaved caspase-3, Bax, and Bcl-2. In addition to the western blot, immunofluorescence was used to investigate the expression levels of SIRT1 and PGC-1α. Our results suggest that APN peptide increased cell viability, SOD, and GSH-Px levels and decreased LDH release, ROS and MDA levels, and cell apoptosis. APN peptide upregulated the expression of SIRT1, PGC-1α, and Bcl-2 and downregulated the expression of cleaved caspase-3 and Bax. Furthermore, the protective effects of the APN peptide were abolished by SIRT1 siRNA. Our findings suggest that APN peptide protects HT22 neurons against Glu-induced injury by inhibiting neuronal apoptosis and activating SIRT1-dependent PGC-1α signaling.

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Section: Discussionsupporting

confidence: 70%

Adiponectin Protects against Glutamate‐Induced Excitotoxicity via Activating SIRT1‐Dependent PGC‐1α Expression in HT22 Hippocampal Neurons

Liang

Zhao

Liu

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…These results suggested that SIRT1 influences the expression of its target PGC‐1α. Indeed, several previous studies have demonstrated that SIRT1 can enhance PGC‐1α activation and make it act as a substrate of deacetylation …”

Section: Discussionmentioning

confidence: 99%

Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia

Nishigaki

Kido

Kida

et al. 2020

Reprod Medicine & Biology

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Purpose Resveratrol is a well‐known potent activator of sirtuin‐1 (SIRT1). We investigated the direct effects of hypoxia and resveratrol on SIRT1/ peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α) pathways, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor (HIF)‐1α, and mitochondrial quantity in a steroidogenic human ovarian granulosa‐like tumor cell line (KGN) cells. Methods KGN cells were cultured with cobalt chloride (CoCl2; a hypoxia‐mimicking agent) and/or resveratrol. The mRNA and protein levels, protein secretion, and intracellular localization were assessed by real‐time PCR, Western blot analysis, ELISA, and immunofluorescence staining, respectively. Mitochondrial quantity was measured based on the mitochondrial DNA (mtDNA) copy number. Results CoCl2 simultaneously attenuated the levels of SIRT1 and mtDNA expression, and induced the levels of VEGF protein production. In contrast, resveratrol significantly increased the levels of SIRT1 and mtDNA copy number, but reduced VEGF production in normoxia. Resveratrol could recover CoCl2‐suppressed SIRT1 and mtDNA expression and antagonize CoCl2‐induced VEGF production. CoCl2 treatment resulted in a downregulation of PGC‐1α expression, and this effect was recovered by resveratrol. Resveratrol significantly suppressed the production of the CoCl2‐induced HIF‐1α and VEGF proteins. Conclusion These results suggest that resveratrol improves mitochondrial quantity by activating the SIRT1/PGC‐1α pathway and inhibits VEGF induction through HIF‐1α under hypoxic conditions.

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“…Mitochondria also influence the activities of intestinal functional effector cells, such as immune cells, epithelial cells and enterochromaffin cells (Cunningham et al, 2016). These same cells, on the other hand, are under the influence of the gut microbiota, whose contributing role in mitochondria functions is becoming evident.…”

Section: Introductionmentioning

confidence: 99%

The Crosstalk between the Gut Microbiota and Mitochondria during Exercise

Clark¹,

Mach²

2017

Front. Physiol.

253

216

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Many physiological changes occur in response to endurance exercise in order to adapt to the increasing energy needs, mitochondria biogenesis, increased reactive oxygen species (ROS) production and acute inflammatory responses. Mitochondria are organelles within each cell that are crucial for ATP production and are also a major producer of ROS and reactive nitrogen species during intense exercise. Recent evidence shows there is a bidirectional interaction between mitochondria and microbiota. The gut microbiota have been shown to regulate key transcriptional co-activators, transcription factors and enzymes involved in mitochondrial biogenesis such as PGC-1α, SIRT1, and AMPK genes. Furthermore, the gut microbiota and its metabolites, such as short chain fatty acids and secondary bile acids, also contribute to host energy production, ROS modulation and inflammation in the gut by attenuating TNFα- mediated immune responses and inflammasomes such as NLRP3. On the other hand, mitochondria, particularly mitochondrial ROS production, have a crucial role in regulating the gut microbiota via modulating intestinal barrier function and mucosal immune responses. Recently, it has also been shown that genetic variants within the mitochondrial genome, could affect mitochondrial function and therefore the intestinal microbiota composition and activity. Diet is also known to dramatically modulate the composition of the gut microbiota. Therefore, studies targeting the gut microbiota can be useful for managing mitochondrial related ROS production, pro-inflammatory signals and metabolic limits in endurance athletes.

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Peroxisome Proliferator-activated Receptor-γ Coactivator 1-α (PGC1α) Protects against Experimental Murine Colitis

Cited by 75 publications

References 72 publications

Adiponectin Protects against Glutamate‐Induced Excitotoxicity via Activating SIRT1‐Dependent PGC‐1α Expression in HT22 Hippocampal Neurons

Adiponectin Protects against Glutamate‐Induced Excitotoxicity via Activating SIRT1‐Dependent PGC‐1α Expression in HT22 Hippocampal Neurons

Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia

The Crosstalk between the Gut Microbiota and Mitochondria during Exercise

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