Down regulation of Peroxiredoxin-3 in 3T3-L1 adipocytes leads to oxidation of Rictor in the mammalian-target of rapamycin complex 2 (mTORC2)

Olson, Dalay H.; Burrill, Joel S.; Kuzmicic, Jovan; Hahn, Wendy S.; Park, Ji‐Man; Kim, Do-Hyung; Bernlohr, David A.

doi:10.1016/j.bbrc.2017.09.171

Cited by 6 publications

(2 citation statements)

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“…Mitochondrial ROS overload is restored to normal upon Nox4 silencing implying the causative role of enhanced Nox4 activity in Parp3-deficient astrocytes. Importantly, mitochondrially-derived oxidative stress has been implicated in the oxidation of Rictor resulting in the inactivation of mTorc2 and impaired Akt(S473) phosphorylation 65 . Consistently, our findings reveal that increased Nox4-generated ROS leads to dysfunctional mTorc2 signaling including attenuation of Akt(S473) phosphorylation during astrocytic differentiation of Parp3 –/ – NPSCs.…”

Section: Discussionmentioning

confidence: 99%

Parp3 promotes astrocytic differentiation through a tight regulation of Nox4-induced ROS and mTorc2 activation

et al. 2020

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Parp3 is a member of the Poly(ADP-ribose) polymerase (Parp) family that has been characterized for its functions in strand break repair, chromosomal rearrangements, mitotic segregation and tumor aggressiveness. Yet its physiological implications remain unknown. Here we report a central function of Parp3 in the regulation of redox homeostasis in continuous neurogenesis in mice. We show that the absence of Parp3 provokes Nox4-induced oxidative stress and defective mTorc2 activation leading to inefficient differentiation of post-natal neural stem/progenitor cells to astrocytes. The accumulation of ROS contributes to the decreased activity of mTorc2 as a result of an oxidation-induced and Fbxw7-mediated ubiquitination and degradation of Rictor. In vivo, mTorc2 signaling is compromised in the striatum of naïve post-natal Parp3-deficient mice and 6 h after acute hypoxia-ischemia. These findings reveal a physiological function of Parp3 in the tight regulation of striatal oxidative stress and mTorc2 during astrocytic differentiation and in the acute phase of hypoxia-ischemia.

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Section: Discussionmentioning

confidence: 99%

Parp3 promotes astrocytic differentiation through a tight regulation of Nox4-induced ROS and mTorc2 activation

et al. 2020

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“…In brown adipocytes, a reduced mTOR activity stimulates mitophagy, which is essential for thermogenesis [ 126 ]. In 3T3-L1 adipocytes, mitochondrial dysfunction may attenuate insulin signaling through the oxidation of Rictor in the mammalian target of mTORC2 [ 127 ]. As an important lipid metabolic organ, the liver is the main place for adipogenesis and lipid oxidation, and impaired lipid metabolism in the liver is closely related to obesity [ 128 , 129 ].…”

Section: Mtor and Obesitymentioning

confidence: 99%

Targeting mTOR Signaling by Dietary Polyphenols in Obesity Prevention

Cao

Han

et al. 2022

Nutrients

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Dietary polyphenols can be utilized to treat obesity and chronic disorders linked to it. Dietary polyphenols can inhibit pre-adipocyte proliferation, adipocyte differentiation, and triglyceride accumulation; meanwhile, polyphenols can also stimulate lipolysis and fatty acid β-oxidation, but the molecular mechanisms of anti-obesity are still unclear. The mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cell growth, survival, metabolism, and immunity. mTOR signaling is also thought to play a key role in the development of metabolic diseases such as obesity. Recent studies showed that dietary polyphenols could target mTOR to reduce obesity. In this review, we systematically summarized the research progress of polyphenols in preventing obesity through the mTOR signaling pathway. Mechanistically, polyphenols can target multiple signaling pathways and gut microbiota to regulate the mTOR signaling pathway to exert anti-obesity effects. The main mechanisms include: modulating lipid metabolism, adipogenesis, inflammation, etc. Dietary polyphenols exerting an anti-obesity effect by targeting mTOR signaling will broaden our understanding of the anti-obesity mechanisms of polyphenols and provide valuable insights for researchers in this novel field.

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