Resveratrol ameliorates disorders of mitochondrial biogenesis and mitophagy in rats continuously exposed to benzo(a)pyrene from embryonic development through adolescence

Chen, Kai-Ge; Kang, Run-Run; Sun, Qian; Liu, Chang; Ma, Zhuo; Liu, Kuan; Deng, Yu; Liu, Wei; Xu, Bin

doi:10.1016/j.tox.2020.152532

Cited by 22 publications

(6 citation statements)

References 35 publications

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“…Like ancient Chinese philosophy "Ying" and "Yang, " both generation of newly synthesized mitochondria, by mitochondrial biogenesis, and elimination of detrimental and/or superfluous mitochondria, by mitophagy, are predominantly required for maintaining mitochondrial homeostasis. Recent findings have hinted that any abnormality in these two opposing processes can influence the quantity and quality of mitochondria, which will further affect mitochondrial function and the ability of cells to adjust their mitochondrial networks in response to physiological adaptations and stress conditions (Palikaras et al, 2015;Singh et al, 2018;Wang et al, 2019;Yau et al, 2019;Zhou et al, 2019;Chen et al, 2020). At the same time, impaired mitochondrial function and homeostasis are now widely accepted to be associated with multiple aspects of the aging process and age-onset diseases (Lopez-Otin et al, 2013;Mattson and Arumugam, 2018;Akbari et al, 2019).…”

Section: A Balanced Act Of Mitochondrial Biogenesis and Mitophagymentioning

confidence: 99%

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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Mitochondrial function is multifaceted in response to cellular energy homeostasis and metabolism, with the generation of adenosine triphosphate (ATP) through the oxidative phosphorylation (OXPHOS) being one of their main functions. Selective elimination of mitochondria by mitophagy, in conjunction with mitochondrial biogenesis, regulates mitochondrial function that is required to meet metabolic demand or stress response. Growth hormone (GH) binds to the GH receptor (GHR) and induces the JAK2/STAT5 pathway to activate the synthesis of insulin-like growth factor 1 (IGF1). The GH–GHR–IGF1 axis has been recognized to play significant roles in somatic growth, including cell proliferation, differentiation, division, and survival. In this review, we describe recent discoveries providing evidence for the contribution of the GH–GHR–IGF1 axis on mitochondrial biogenesis, mitophagy (or autophagy), and mitochondrial function under multiple physiological conditions. This may further improve our understanding of the effects of the GH–GHR–IGF1 axis on mitochondrial function, which may be controlled by the delicate balance between mitochondrial biogenesis and mitophagy. Specifically, we also highlight the challenges that remain in this field.

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Section: A Balanced Act Of Mitochondrial Biogenesis and Mitophagymentioning

confidence: 99%

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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“…This hepatic impairment of the LKB1/AMPK pathway and induction of the mTOR/lipogenesis pathway in HFD-obese rats is coupled with significant suppression in the mitochondrial biogenesis pathway, as indicated by downregulation of the main components of the pathway, namely, PGC-1α, NRF1, and Tfam at both mRNA and protein levels. This pathway is essential for the maintenance of mitochondrial biogenesis and homeostasis, enhancement of mitochondrial capacity, and fatty acid oxidation [ 36 ]. In line with these data, Lei and his colleagues documented decreased hepatic expression of PGC-1α, NRF1, and Tfam in the NAFLD human liver, suggesting a key role in mitochondrial biogenesis [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

The Anti-Obesity and Anti-Steatotic Effects of Chrysin in a Rat Model of Obesity Mediated through Modulating the Hepatic AMPK/mTOR/lipogenesis Pathways

et al. 2023

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Background: Obesity is a complex multifactorial disease characterized by excessive adiposity, and is linked to an increased risk of nonalcoholic fatty liver disease (NAFLD). Flavonoids are natural polyphenolic compounds that exert interesting pharmacological effects as antioxidant, anti-inflammatory, and lipid-lowering agents. In the present study, we investigated the possible therapeutic effects of the flavonoid chrysin on obesity and NAFLD in rats, and the role of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways in mediating these effects. Method: Thirty-two Wistar male rats were divided into two groups: the control group and the obese group. Obesity was induced by feeding with an obesogenic diet for 3 months. The obese rats were subdivided into four subgroups, comprising an untreated group, and three groups treated orally with different doses of chrysin (25, 50, and 75 mg/kg/day for one month). Results revealed that chrysin treatment markedly ameliorated the histological changes and significantly and dose-dependently reduced the weight gain, hyperglycemia, and insulin resistance in the obese rats. Chrysin, besides its antioxidant boosting effects (increased GSH and decreased malondialdehyde), activated the AMPK pathway and suppressed the mTOR and lipogenic pathways, and stimulated expression of the genes controlling mitochondrial biogenesis in the hepatic tissues in a dose-dependent manner. In conclusion, chrysin could be a promising candidate for the treatment of obesity and associated NAFLD, aiding in attenuating weight gain and ameliorating glucose and lipid homeostasis and adipokines, boosting the hepatic mitochondrial biogenesis, and modulating AMPK/mTOR/SREBP-1c signaling pathways.

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“…This effect could be linked to the resveratrol-induced decrease of Miro2 and Mfn2 levels observed in parkin-mutant fibroblasts. Thus, the resveratrol treatment, by modulating specific signaling pathways such as AMPK//SIRT1/PGC1α [131], might lead to an increase of autophagic flux and mitochondrial biogenesis (see [5,131]), driving to the formation of new healthy mitochondria and to the proper cAMP and MAM proteins levels. This pathway could also be linked to Ca 2+ homeostasis; indeed, in colon cancer cells it has been shown that resveratrol induces a metabolic reprogramming, increasing oxidative capacities, pyruvate dehydrogenase activity, and ATP production.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Treatment in Human Parkin-Mutant Fibroblasts Modulates cAMP and Calcium Homeostasis Regulating the Expression of Mitochondria-Associated Membranes Resident Proteins

et al. 2021

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Parkin plays an important role in ensuring efficient mitochondrial function and calcium homeostasis. Parkin-mutant human fibroblasts, with defective oxidative phosphorylation activity, showed high basal cAMP level likely ascribed to increased activity/expression of soluble adenylyl cyclase and/or low expression/activity of the phosphodiesterase isoform 4 and to a higher Ca2+ level. Overall, these findings support the existence, in parkin-mutant fibroblasts, of an abnormal Ca2+ and cAMP homeostasis in mitochondria. In our previous studies resveratrol treatment of parkin-mutant fibroblasts induced a partial rescue of mitochondrial functions associated with stimulation of the AMPK/SIRT1/PGC-1α pathway. In this study we provide additional evidence of the potential beneficial effects of resveratrol inducing an increase in the pre-existing high Ca2+ level and remodulation of the cAMP homeostasis in parkin-mutant fibroblasts. Consistently, we report in these fibroblasts higher expression of proteins implicated in the tethering of ER and mitochondrial contact sites along with their renormalization after resveratrol treatment. On this basis we hypothesize that resveratrol-mediated enhancement of the Ca2+ level, fine-tuned by the ER–mitochondria Ca2+ crosstalk, might modulate the pAMPK/AMPK pathway in parkin-mutant fibroblasts.

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Resveratrol ameliorates disorders of mitochondrial biogenesis and mitophagy in rats continuously exposed to benzo(a)pyrene from embryonic development through adolescence

Cited by 22 publications

References 35 publications

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

The Anti-Obesity and Anti-Steatotic Effects of Chrysin in a Rat Model of Obesity Mediated through Modulating the Hepatic AMPK/mTOR/lipogenesis Pathways

Resveratrol Treatment in Human Parkin-Mutant Fibroblasts Modulates cAMP and Calcium Homeostasis Regulating the Expression of Mitochondria-Associated Membranes Resident Proteins

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