A multi‐organ analysis of the role of <scp>mTOR</scp> in fetal alcohol spectrum disorders

Carabulea, Alexander L; Janeski, Joseph D; Naik, Vishal D.; Chen, Kang; Mor, Gil; Ramadoss, Jayanth

doi:10.1096/fj.202201865r

Cited by 4 publications

(7 citation statements)

References 57 publications

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“…4E-BP is an inhibitor of eIF4E, which is related to protein synthesis, and mTORC1 inhibition of 4E-BP can promote protein synthesis. Activation of mTORC1 on eIF4B and S6 can promote protein synthesis [ 36 ]. Meanwhile, mTORC2 signaling pathway can be activated.…”

Section: Discussionmentioning

confidence: 99%

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Amin,

Yu,

et al. 2024

Foods

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Dietary protein supplementation has emerged as a promising strategy in combating sarcopenia. Furthermore, searching for alternatives of animal proteins has been a hot topic. The present study aimed to investigate the effects of zein peptides on C2C12 myoblasts and explore their potential molecular mechanisms. The proliferative, cell cycle, and anti-apoptotic activities of zein peptides were evaluated. Peptidomics analysis and transcriptome sequencing were employed to explore the structure-activity relationship and underlying molecular mechanisms. The results indicated that zein peptides (0.05–0.2 mg/mL) exerted a significant proliferation-promoting impact on C2C12 cells, via increasing cell viability by 33.37 to 42.39%. Furthermore, zein peptides significantly increased S phase proportion and decreased the apoptosis rate from 34.08% (model group) to 28.96% in C2C12 cells. In addition, zein peptides exhibited a pronounced anti-apoptotic effect on C2C12 cells. Zein peptides are abundant in branch-chain amino acids, especially leucine. Transcriptomics analysis revealed that zein peptides can promote proliferation, accelerate cell cycle, and improve protein synthesis of muscle cells through mTORC1 and mTORC2 signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Amin,

Yu,

et al. 2024

Foods

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“…In contrast, little is known about mTORC2 although it is possible that mTORC2 may have some regulating effect on mTORC1 system ( Liu and Sabatini, 2020 ; Szwed et al, 2021 ). mTORC1 directly promotes protein synthesis by ultimately phosphorylating the Eukaryotic Translation Initiation Factor 4E-binding Proteins (4E-BPs), as well as Ribosomal Protein S6 Kinase 1 (S6K1; Carabulea et al, 2023 ). Others have shown that nicotine significantly reduced hyperalgesia in mice that received acute/repeated rapamycin injections, and nicotine reversed the outcomes of rapamycin on the phosphorylation of 4E-BP1 and S6K ( Li S. et al, 2019 ; Li Y. et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…mTOR plays an integral role in modulating brain anabolic and catabolic activities, including protein synthesis and autophagy. mTOR is a 289-kDa serine/threonine protein kinase that makes up the catalytic subunit of two individual complexes, known as mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2; Carabulea et al, 2023 ). mTORC1 plays a major role in multiple cellular signals to sense the availability of nutrients, growth factors, and energy to promote cellular growth and catabolic activity during stress, whereas less is known about mTORC2 ( Carabulea et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…mTOR is a 289-kDa serine/threonine protein kinase that makes up the catalytic subunit of two individual complexes, known as mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2; Carabulea et al, 2023 ). mTORC1 plays a major role in multiple cellular signals to sense the availability of nutrients, growth factors, and energy to promote cellular growth and catabolic activity during stress, whereas less is known about mTORC2 ( Carabulea et al, 2023 ). During fetal and neonatal brain development, mTOR signaling system plays critical roles in neuron differentiation, growth, and neuronal proliferation, and in homeostasis of stem cell and progenitor cell population ( Easley et al, 2010 ; Lee, 2015 ), and its disruption has been associated with smaller brain size with fewer neurons and neural progenitors ( Kim, 2015 ), translation dysregulation, and altered neuroprotection mediated by autophagy ( Carabulea et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…mTORC1 plays a major role in multiple cellular signals to sense the availability of nutrients, growth factors, and energy to promote cellular growth and catabolic activity during stress, whereas less is known about mTORC2 ( Carabulea et al, 2023 ). During fetal and neonatal brain development, mTOR signaling system plays critical roles in neuron differentiation, growth, and neuronal proliferation, and in homeostasis of stem cell and progenitor cell population ( Easley et al, 2010 ; Lee, 2015 ), and its disruption has been associated with smaller brain size with fewer neurons and neural progenitors ( Kim, 2015 ), translation dysregulation, and altered neuroprotection mediated by autophagy ( Carabulea et al, 2023 ). Very little is known about effects of e-cig vaping on the mTOR system in the developing brain, and we herein aimed to discern how e-cig vaping may affect fetal hippocampal mTOR signaling in order to further elucidate developmental hippocampal effects.…”

Section: Introductionmentioning

confidence: 99%

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Impact of e-cigarette vaping aerosol exposure in pregnancy on mTOR signaling in rat fetal hippocampus

et al. 2023

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Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and many view them as less harmful and may help quit or reduce combustible cigarettes. Implementing a state-of-the-art engineered vaping system, comprising an atomizer similar to those sold in vape shops, we aimed to utilize a translational e-cig inhalation delivery method to provide crucial information on the impact of prenatal e-cig aerosols on the developing brain hippocampal mTOR system in a rat model system. Gestational e-cig vaping significantly increased P-mTOR levels (p < 0.05) in the rat fetal hippocampi in the nicotine group (comprising of VG/PG + nicotine) compared to the control and the juice (comprising of VG/PG) groups. Total mTOR expression was not different among groups. Immunofluorescence imaging demonstrated P-mTOR was detected exclusively in the granule cells of the dentate gyrus of the fetal hippocampus. E-cig did not alter DEPTOR, but RAPTOR and RICTOR were higher (p < 0.05) in the Nicotine group. Gestational e-cig vaping with nicotine increased (p < 0.05) the activity and expression of 4EBP1, p70S6K, but decreased (p < 0.05) P-PKCα in the fetal hippocampi. In summary, dysregulation of mTORC1 and the related mTORC2, their activity, and downstream proteins together may play a critical role in e-cig-vaping-induced neurobiological phenotypes during development.

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The Impact of Oxidative Stress on the Epigenetics of Fetal Alcohol Spectrum Disorders

Terracina,

Tarani,

Ceccanti

et al. 2024

Preprint

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Fetal Alcohol Spectrum Disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The “spectrum” of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments, which can have profound and lasting effects on individuals throughout their lives impacting their health, social interactions, psychological well-being and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions' efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress on epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.

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A multi‐organ analysis of the role of mTOR in fetal alcohol spectrum disorders

Cited by 4 publications

References 57 publications

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Impact of e-cigarette vaping aerosol exposure in pregnancy on mTOR signaling in rat fetal hippocampus

The Impact of Oxidative Stress on the Epigenetics of Fetal Alcohol Spectrum Disorders

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