Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake

Kobylewski, Sarah; Henderson, Kimberly A.; Yamada, Kristin; Eckhert, Curtis D.

doi:10.1007/s12011-016-0824-y

Cited by 39 publications

(17 citation statements)

References 88 publications

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“…Higher expression of HSP90B1 was associated with poor prognosis in non-small cell lung cancer patients[ 78 ] but the regulation of this gene during the progression of the prostate cancer is not yet known. There are, however, reports on how this gene is affected when the androgen-sensitive LNCaP and the androgen-insensitive prostate cancer cell lines are treated with androgen[ 79 ] or boric acid[ 80 ].…”

Section: Comparing Individual Genes In Two or More Phenotypesmentioning

confidence: 99%

Powerful quantifiers for cancer transcriptomics

Iacobaş

2020

WJCO

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Every day, investigators find a new link between a form of cancer and a particular alteration in the sequence or/and expression level of a key gene, awarding this gene the title of “biomarker”. The clinician may choose from numerous available panels to assess the type of cancer based on the mutation or expression regulation (“transcriptomic signature”) of “driver” genes. However, cancer is not a “one-gene show” and, together with the alleged biomarker, hundreds other genes are found as mutated or/and regulated in cancer samples. Regardless of the platform, a well-designed transcriptomic study produces three independent features for each gene: Average expression level, expression variability and coordination with expression of each other gene. While the average expression level is used in all studies to identify what genes were up-/down-regulated or turn on/off, the other two features are unfairly ignored. We use all three features to quantify the transcriptomic change during the progression of the disease and recovery in response to a treatment. Data from our published microarray experiments on cancer nodules and surrounding normal tissue from surgically removed tumors prove that the transcriptomic topologies are not only different in histopathologically distinct regions of a tumor but also dynamic and unique for each human being. We show also that the most influential genes in cancer nodules [the Gene Master Regulators (GMRs)] are significantly less influential in the normal tissue. As such, “smart” manipulation of the cancer GMRs expression may selectively kill cancer cells with little consequences on the normal ones. Therefore, we strongly recommend a really personalized approach of cancer medicine and present the experimental procedure and the mathematical algorithm to identify the most legitimate targets (GMRs) for gene therapy.

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Section: Comparing Individual Genes In Two or More Phenotypesmentioning

confidence: 99%

Powerful quantifiers for cancer transcriptomics

Iacobaş

2020

WJCO

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“…Activating transcription factor 4 (ATF4) is the main component that encodes the cAMP response element-binding transcription factor, stimulating cell survival via modulation of redox reactions, stress response, protein synthesis, and secretion [ 62 , 63 ]. ATF4 is triggered by stress signals such as anoxia/hypoxia, amino acid abstinence, endoplasmic reticulum stress, and oxidative stress [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Different Doses of β‐Cryptoxanthin May Secure the Retina from Photooxidative Injury Resulted from Common LED Sources

Orhan

Tuzcu

Gençoğlu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Retinal damage associated with loss of photoreceptors is a hallmark of eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Potent nutritional antioxidants were previously shown to abate the degenerative process in AMD. β-Cryptoxanthin (BCX) is an essential dietary carotenoid with antioxidant, anti-inflammatory, and provitamin A activity. It is a potential candidate for developing intervention strategies to delay the development/progression of AMD. In the current study, the effect of a novel, highly purified BCX oral formulation on the rat retinal damage model was evaluated. Rats were fed with BCX for four weeks at the doses of 2 and 4 mg/kg body weight in the form of highly bioavailable oil suspension, followed by retinal damage by exposing to the bright light-emitting diode (LED) light (750 lux) for 48 hrs. Animals were sacrificed after 48 hours, and eyes and blood samples were collected and analyzed. BCX supplementations (2 and 4 mg/kg) showed improvements in the visual condition as demonstrated by histopathology of the retina and measured parameters such as total retinal thickness and outer nuclear layer thickness. BCX supplementation helped reduce the burden of oxidative stress as seen by decreased serum and retinal tissue levels of malondialdehyde (MDA) and restored the antioxidant enzyme activities in BCX groups. Further, BCX supplementation modulated inflammatory markers (IL-1β, IL-6, and NF-κB), apoptotic proteins (Bax, Bcl-2, caspase 3), growth proteins and factors (GAP43, VEGF), glial and neuronal proteins (GFAP, NCAM), and heme oxygenase-1 (HO-1), along with the mitochondrial stress markers (ATF4, ATF6, Grp78, Grp94) in the rat retinal tissue. This study indicates that oral supplementation of BCX exerts a protective effect on light-induced retinal damage in the rats via reducing oxidative stress and inflammation, also protected against mitochondrial DNA damage and cellular death.

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“…Recent studies have demonstrated that the toxic peptide, Aβ, induces ERS and then activates the unfolded protein response (8,13). It has been reported that ERS is involved in the cleavage of Aβ protein precursor, thus promoting the production of Aβ and facilitating the development of AD (14–16). The results of the present study revealed that treatment with 20 mM Aβ 25-35 for 24 h contributed to the unbalancing of the redox state by reducing SOD activity, and increasing MDA content and ROS accumulation in PC12 cells, consistent with previous studies (17,18).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV ameliorates endoplasmic reticulum stress‑induced apoptosis of Aβ25‑35‑treated PC12 cells by inhibiting the p38�MAPK signaling pathway

2019

Mol Med Report

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Endoplasmic reticulum stress (ERS) serves a vital role in the pathological development of Alzheimer's disease (AD). ERS can promote programmed cell death (apoptosis) during AD; however, the specific molecular mechanisms that lead to ERS remain unclear. It is very important that a drug for the treatment of AD is identified. Our previous studies indicated that astragaloside IV (AST IV) has anti-inflammatory effects and helps cells resist oxidative stress. In the present study, western blotting and reverse transcription semi-quantitative polymerase chain reaction were used to detect protein and mRNA expression levels, flow cytometry was used to measure intracellular reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) and malondialdehyde (MDA) activity was detected using commercially available kits. The results demonstrated that SOD activity was decreased, and MDA content, ROS levels, and the expression levels of p38 mitogen-activated protein kinase (MAPK) and ERS-associated proteins, including binding immunoglobulin protein/glucose-regulated protein and growth arrest- and DNA damage -inducible gene 153/C/EBP homologous protein, were increased in amyloid β (Aβ) 25-35 -treated PC12 cells. Furthermore, to investigate the role of p38 MAPK and the effects of AST IV in an in vitro model of AD, SB203580, a p38 MAPK signaling pathway inhibitor, and AST IV were administered to Aβ 25-35 -treated PC12 cells. The results revealed that AST IV protected the cells against AD. This effect may be caused by decreases in ROS levels, which may inhibit the p38 MAPK signaling pathway and thereby suppress ERS in Aβ 25-35 -treated PC12 cells.

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Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake

Cited by 39 publications

References 88 publications

Powerful quantifiers for cancer transcriptomics

Powerful quantifiers for cancer transcriptomics

Different Doses of β‐Cryptoxanthin May Secure the Retina from Photooxidative Injury Resulted from Common LED Sources

Astragaloside IV ameliorates endoplasmic reticulum stress‑induced apoptosis of Aβ25‑35‑treated PC12 cells by inhibiting the p38�MAPK signaling pathway

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