Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress

Li, Dan; Shao, Rong; Wang, Na; Zhou, Nan; Du, Kaili; Shi, Jiahui; Wang, Yihan; Zhao, Zhuangzhuang; Ye, Xin; Zhang, Xiaoli; Xu, Haoxing

doi:10.1080/15548627.2020.1739442

Cited by 100 publications

(65 citation statements)

References 53 publications

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“…This alteration can damage mitochondrial function, causing higher reactive oxygen species production ( Brunetta et al, 2020 ). SFN has been proven to be an effective compound that prevents oxidative stress through the activation of Nrf2 (D. Li et al, 2020 ). Pgc-1 α and Nrf2 were two of the important modulating factors in mitochondrial biogenesis ( Kasai et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects of Sulforaphane on High-Fat Diet-Induced Obesity in Mice Through Browning of White Fat

Liu

Chen

et al. 2021

Front. Pharmacol.

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Background: Sulforaphane (SFN), an isothiocyanate naturally occurring in cruciferous vegetables, is a potent indirect antioxidant and a promising agent for the control of metabolic disorder disease. The glucose intolerance and adipogenesis induced by diet in rats was inhibited by SFN. Strategies aimed at induction of brown adipose tissue (BAT) could be a potentially useful way to against obesity. However, in vivo protective effect of SFN against obesity by browning white adipocyte has not been reported. Our present study is aimed at evaluation the efficacy of the SFN against the high-fat induced-obesity mice and investigating the potential mechanism.Methods: High-Fat Diet-induced obese female C57BL/6 mice were intraperitoneally injected with SFN (10 mg/kg) daily. Body weight was recorded every 3 days. 30 days later, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. At the end of experiment, fat mass were measured and the adipogenesis as well as browning associated genes expression in white adipose tissue (WAT) were determined by RT-qPCR and western blot. Histological examination of the adipose tissue samples were carried out with hematoxylin–eosin (HE) staining and immunofluorescence staining method. In vitro, pre-adipocytes C3H10T1/2 were treated with SFN to investigate the direct effects on adipogenesis.Results: SFN suppressed HFD-induced body weight gain and reduced the size of fat cells in mice. SFN suppressed the expression of key genes in adipogenesis, inhibited lipid accumulation in C3H10T1/2 cells, increased the expression of brown adipocyte-specific markers and mitochondrial biogenesis in vivo and in vitro, and decreased cellular and mitochondrial oxidative stress. These results suggested that SFN, as a nutritional factor, has great potential role in the battle against obesity by inducing the browning of white fat.Conclusion: SFN could significantly decrease the fat mass, and improve glucose metabolism and increase insulin sensitivity of HFD-induced obese mice by promoting the browning of white fat and enhancing the mitochondrial biogenesis in WAT. Our study proves that SFN could serve as a potential medicine in anti-obesity and related diseases.

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Section: Discussionmentioning

confidence: 99%

The Protective Effects of Sulforaphane on High-Fat Diet-Induced Obesity in Mice Through Browning of White Fat

Liu

Chen

et al. 2021

Front. Pharmacol.

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“…According to its important role in promoting autophagy and lysosome, TFEB has become an important therapeutic target for diseases involving excess ROS and autophagy dysfunction, such as AD, PD, and atherosclerosis (see Figure 2 for details about TFEB and autophagy). Recently, several TFEB agonists have been identified and preclinical or clinical trials are applied [71,72]. release and calcineurin activation.…”

Section: Ros and Autophagymentioning

confidence: 99%

“…[42]. Nrf2 activators, i.e., sulforaphane, show their protective effect against oxidative stress based on the Nrf2 signaling cascade [72]. (b) FoxO pathway: once activated by ROS, FoxO (mainly FoxO1 and FoxO3) transfers to the nucleus to initiate transcriptional activity [48].…”

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confidence: 99%

Reactive Oxygen Species as a Link between Antioxidant Pathways and Autophagy

Ding

et al. 2021

Oxidative Medicine and Cellular Longevity

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Reactive oxygen species (ROS) are highly reactive molecules that can oxidize proteins, lipids, and DNA. Under physiological conditions, ROS are mainly generated in the mitochondria during aerobic metabolism. Under pathological conditions, excessive ROS disrupt cellular homeostasis. High levels of ROS result in severe oxidative damage to the cellular machinery. However, a low/mild level of ROS could serve as a signal to trigger cell survival mechanisms. To prevent and cope with oxidative damage to biomolecules, cells have developed various antioxidant and detoxifying mechanisms. Meanwhile, ROS can initiate autophagy, a process of self-clearance, which helps to reduce oxidative damage by engulfing and degrading oxidized substance. This review summarizes the interactions among ROS, autophagy, and antioxidant pathways. The effects of natural phytochemicals on autophagy induction, antioxidation, and dual-function are also discussed.

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“…2′,7′-Dichlorofluorescin diacetate (DCFH-DA, Sigma-Aldrich, 35848) was used as an ROS capturing reagent as previously described ( Zhou et al, 2016 ; Li et al, 2021 ). Briefly, cells were incubated with 5 μM DCFH-DA in serum-free culture media at 37°C for 1 h, and washed with PBS before flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis

Zhang

Chen

Sun

et al. 2021

Front. Cell Dev. Biol.

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Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis and reduced bone formation was the main pathological change in GIOP. Our previous studies have shown that there was an imbalance between adipogenic and osteogenic differentiation in GIOP BM-MSCs and peroxisome proliferator-activated receptor γ2 (PPARγ2) played a vital role in this disorders. Here, we reported that there was an increase in ROS level and SENP3 expression in Dex-induced osteoporotic BM-MSCs, and enhanced adipogenesis and weakened osteogenesis in osteoporotic BM-MSCs might be caused by upregulated SENP3. Then we found that SENP3 de-SUMOylated PPARγ2 on K107 site to potentiate adipogenesis and weaken osteogenesis. These results may provide new strategy and target in the clinical diagnosis and treatment of GIOP.

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Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress

Cited by 100 publications

References 53 publications

The Protective Effects of Sulforaphane on High-Fat Diet-Induced Obesity in Mice Through Browning of White Fat

The Protective Effects of Sulforaphane on High-Fat Diet-Induced Obesity in Mice Through Browning of White Fat

Reactive Oxygen Species as a Link between Antioxidant Pathways and Autophagy

SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis

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