Activation of forkhead box O3a by mono(2‐ethylhexyl)phthalate and its role in protection against mono(2‐ethylhexyl)phthalate‐induced oxidative stress and apoptosis in human cardiomyocytes

2020 ◽  
Author(s):  
Zeze Wang ◽  
Yi Liu ◽  
Xuehui Liu ◽  
Lixiao Zhou ◽  
Xindi Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Human Cardiomyocytes ◽  
Forkhead Box ◽  
Ethylhexyl Phthalate ◽  
Forkhead Box O3a

scholarly journals Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Inah Hwang ◽  
Hiroki Uchida ◽  
Ziwei Dai ◽  
Fei Li ◽  
Teresa Sanchez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Environmental Changes ◽  
Type I ◽  
Neurogenic Differentiation ◽  
Forkhead Box ◽  
Nuclear Lamin ◽  
Neural Stem Progenitor Cells ◽  
Subsequent Activation ◽  
Methyl Group Transfer

AbstractNeural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes like elevated oxidative stress. But how oxidative stress regulates NSPC and its neurogenic differentiation is less clear. Here we report that acutely elevated cellular oxidative stress in NSPCs modulates neurogenic differentiation through induction of Forkhead box protein O3 (FOXO3)-mediated cGAS/STING and type I interferon (IFN-I) responses. We show that oxidative stress activates FOXO3 and its transcriptional target glycine-N-methyltransferase (GNMT) whose upregulation triggers depletion of s-adenosylmethionine (SAM), a key co-substrate involved in methyl group transfer reactions. Mechanistically, we demonstrate that reduced intracellular SAM availability disrupts carboxymethylation and maturation of nuclear lamin, which induce cytosolic release of chromatin fragments and subsequent activation of the cGAS/STING-IFN-I cascade to suppress neurogenic differentiation. Together, our findings suggest the FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signaling cascade as a critical stress response program that regulates long-term regenerative potential.

scholarly journals Hepcidin deficiency causes bone loss through interfering with the canonical Wnt/β-catenin pathway via Forkhead box O3a

2020 ◽  
Vol 23 ◽  
pp. 67-76 ◽  
Author(s):  
Guangfei Li ◽  
Hui Zhang ◽  
Jiadong Wu ◽  
Aifei Wang ◽  
Fan Yang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Forkhead Box ◽  
Canonical Wnt ◽  
Forkhead Box O3a

Mono-2-ethylhexyl phthalate (MEHP) promoted lipid accumulation via JAK2/STAT5 and aggravated oxidative stress in BRL-3A cells

2019 ◽  
Vol 184 ◽  
pp. 109611 ◽  
Author(s):  
Yuezhu Zhang ◽  
Shuyue Wang ◽  
Tianyang Zhao ◽  
Liwei Yang ◽  
Shuangyu Guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Accumulation ◽  
Ethylhexyl Phthalate

Encircling granulosa cells protects against di-(2-ethylhexyl)phthalate-induced apoptosis in rat oocytes cultured in vitro

Zygote ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 203-213 ◽  
Author(s):  
Anima Tripathi ◽  
Vivek Pandey ◽  
A.N. Sahu ◽  
Alok K. Singh ◽  
Pawan K. Dubey
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Granulosa Cells ◽  
Mitochondrial Membrane ◽  
Dependent Manner ◽  
Apoptotic Markers ◽  
Induced Apoptosis ◽  
Ethylhexyl Phthalate

SummaryThe present study investigated if the presence of encircling granulosa cells protected against di(2-ethylhexyl)phthalate (DEHP)-induced oxidative stress in rat oocytes cultured in vitro. Denuded oocytes and cumulus–oocyte complexes (COCs) were treated with or without various doses of DEHP (0.0, 25.0, 50.0, 100, 200, 400 and 800 μM) in vitro. Morphological apoptotic changes, levels of oxidative stress and reactive oxygen species (ROS), mitochondrial membrane potential, and expression levels of apoptotic markers (Bcl2, Bax, cytochrome c) were analyzed. Our results showed that DEHP induced morphological apoptotic changes in a dose-dependent manner in denuded oocytes cultured in vitro. The effective dose of DEHP (400 µg) significantly (P>0.05) increased oxidative stress by elevating ROS levels and the mitochondrial membrane potential with higher mRNA expression and protein levels of apoptotic markers (Bax, cytochrome c). Encircling granulosa cells protected oocytes from DEHP-induced morphological changes, increased oxidative stress and ROS levels, as well as increased expression of apoptotic markers. Taken together our data suggested that encircling granulosa cells protected oocytes against DEHP-induced apoptosis and that the presence of granulosa cells could act positively towards the survival of oocytes under in vitro culture conditions and may be helpful during assisted reproductive technique programmes.

scholarly journals Di-(2-ethylhexyl) phthalate (DEHP) inhibits steroidogenesis and induces mitochondria-ROS mediated apoptosis in rat ovarian granulosa cells

2019 ◽  
Vol 8 (3) ◽  
pp. 381-394 ◽  
Author(s):  
Anima Tripathi ◽  
Vivek Pandey ◽  
Alakh N. Sahu ◽  
Alok Singh ◽  
Pawan K. Dubey
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Granulosa Cells ◽  
Ethylhexyl Phthalate

Increased oxidative stress (OS) due to ubiquitous exposure to di-(2-ethylhexyl) phthalate (DEHP) can affect the quality of oocytes by inducing apoptosis and hampering granulosa cell mediated steroidogenesis.

scholarly journals Sex differences in forkhead box O3a signaling response to hindlimb unloading in rat soleus muscle

2018 ◽  
Vol 69 (2) ◽  
pp. 235-244 ◽  
Author(s):  
Toshinori Yoshihara ◽  
Toshiharu Natsume ◽  
Takamasa Tsuzuki ◽  
Shuo-wen Chang ◽  
Ryo Kakigi ◽  
...  
Keyword(s):  
Sex Differences ◽  
Soleus Muscle ◽  
Hindlimb Unloading ◽  
Forkhead Box ◽  
Rat Soleus Muscle ◽  
Forkhead Box O3a

scholarly journals Embryonic exposures to mono-2-ethylhexyl phthalate induce larval steatosis in zebrafish independent of Nrf2a signaling

2020 ◽  
pp. 1-9
Author(s):  
Karilyn E. Sant ◽  
Hadley M. Moreau ◽  
Larissa M. Williams ◽  
Haydee M. Jacobs ◽  
Anna M. Bowsher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatic Steatosis ◽  
Antioxidant Response ◽  
Abnormal Development ◽  
Fish Length ◽  
Peroxisome Proliferator ◽  
Primary Metabolite ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Of Genes ◽  
Ethylhexyl Phthalate

Abstract Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type and nrf2a mutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha target fabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.

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