Nerve growth factor exhibits an antioxidant and an autocrine activity in mouse liver that is modulated by buthionine sulfoximine, arsenic, and acetaminophen

Abstract

Nerve growth factor (NGF) is one of the several structurally related proteins, named neurotrophins (NTs), that regulate neuronal survival, development, function, and plasticity. Moreover, NGF is an important activator of antioxidant mechanisms. These NGF functions are mediated by tropomyosin-related kinase receptor A (TrkA). Although NTs and their receptors have been shown to be expressed in visceral tissues, the extent to which NTs are involved in the physiology of visceral tissues is less clear. NGF is the most expressed NT in adult mouse livers. Although NGF is an important modulator of antioxidant mechanisms in neural tissues, few studies describe the relationship between oxidative stress and NGF expression in the liver. In this study, we demonstrate that ngfb mRNA is positively modulated in mouse livers after oxidative injury via intraperitoneal injection of 14 mg/kg sodium arsenite, 6 mmol/kg L-buthionine-S-R-sulfoximine (BSO), or 300 mg/kg acetaminophen (APAP). In addition to the upregulation of ngfb, we observed the phosphorylation of the NGF high-affinity receptor TrkA in the liver as well as the downstream phosphorylation of Akt, NF-kB nuclear migration and iκbα and tx-1 mRNA upregulation. These effects were abolished when a neutralizing anti-NGF antibody was used. Furthermore, this anti-NGF antibody alone induced oxidative stress in the liver by decreasing the reduced glutathione, increasing the oxidized glutathione, and downregulating tx-1 mRNA. Thus, NGF plays a critical role in liver protection against oxidative stress and xenobiotic injury as well as maintains a reduced thiol state.

PDLLA/PRGD/β‐TCP conduits build the neurotrophin‐rich microenvironment suppressing the oxidative stress and promoting the sciatic nerve regeneration

“…Furthermore, Galeotti put forward that NGF‐mediated decrease of mitochondrial ROS was dependent on the transcriptional up‐regulation of the MnSOD by activating CREB. Valdovinos‐Flores and Gonsebatt revealed that NGF played a critical role in liver protection against oxidative stress through maintaining a reduced thiol state. Also, He and Katusic reported a novel finding that BDNF protected human early endothelial progenitor cells by increasing expression of Mn‐SOD to enhance their antioxidant capacity.…”

DNA damage and oxidative injury are associated with hypomyelination in the corpus callosum of newborn NbnCNS‐del mice

“…Moreover, they can also promote cellular survival, elongation of axons, and myelination of oligodendrocytes and their precursors, in vitro and in lesional paradigms (Linker et al, 2009). Nerve growth factor (NGF) is an important activator of antioxidant mechanisms in neural tissues (Valdovinos-Flores and Gonsebatt, 2013). Brain derived neurotrophic factor (BDNF) can decrease oxidative stress and apoptosis in developing hypothalamic neuronal cells (Boyadjieva and Sarkar, 2013).…”

Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide

“…However, systemic activation of this pathway could induce GSH synthesis in other brain regions such as the cortex and cerebellum at 24 h and 9 days ( Figures 1C,D). Increased levels of GSH were observed in mouse brain homogenates (Limón-Pacheco et al, 2007) and in the cerebellum at 2 h after the administration of L-buthionine-S-R-sulfoximine (BSO), a systemic inhibitor of GSH synthesis, which diminished GSH levels in the liver and kidneys (Limón-Pacheco et al, 2007;Valdovinos-Flores and Gonsebatt, 2013;Garza-Lombó et al, 2018b).…”

“…In addition, there is evidence that NFκB inhibitors diminish the expression of EAAC1 in rats (Tai et al, 2008). Nrf2 and NFκB upregulate the transcription of the nfe2l2 and iκκbα genes, respectively (Valdovinos-Flores and Gonsebatt, 2013;Tonelli et al, 2018) and are considered redox-sensitive switches that activate cellular responses to oxidative stress (Moldogazieva et al, 2018). To investigate whether the activation of these transcription factors was associated with increased amino acid transporter expression and increased GSH levels at 24 h, we measured the transcription of the nfe2l2 and iκκbα genes by quantitative reverse transcription PCR (RT-PCR) at 2, 6 and 24 h in the cortex region.…”