Neurodegeneration from Drugs and Aging‐Derived Free Radicals

Ramkissoon, Annmarie; Shapiro, Alan; Loniewska, Margaret M.; Wells, Peter G.

doi:10.1002/9781118355886.ch10

Cited by 4 publications

(7 citation statements)

References 710 publications

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“…The oxidative stress or the oxidative damage would cause neurodegenerative diseases, including the AD. The oxidative stresses impact on the Keap1-NRF2-ARE signaling pathway to upregulate expression of stress response genes, such as NRF2, KEAP1, SOD1, and ETS1 [64]. The observation is consistent with the theory that the incidence of the AD increases with the aging [65].…”

Section: Accumulation Of Damage From Oxidative Stressessupporting

confidence: 83%

Introductory Chapter: Gene Expression Controlling System and Its Application to Medical Sciences

Uchiumi¹

2019

Gene Expression and Control

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We have learned that genes in mammalian cells are transcribed into messenger RNAs (mRNAs), which are to be translated into polypeptides (proteins). This is known as "Central Dogma." Gene expression must be appropriately maintained to regulate development, differentiation, and proliferation of cells. Imbalances or disturbances in gene expression are sometimes deleterious for living things. For example, steroid and thyroid hormones directly bind to nuclear receptors, which induce expression of specific genes. Recent global analyses of gene transcripts revealed that specific transcription factors (TFs) and their networking systems physiologically correspond to the onset of human diseases, including cancer. In other words, expression of specific genes might have relevance to pathogenesis of diseases. Given that OKSM (Yamanaka) factors convert somatic cells into induced pluripotent stem (iPS) cells, alterations in transcriptional state could affect destiny of the cells. In this chapter, revisiting known TFs, we would argue if transcription controlling strategies could contribute for the novel therapies on human diseases. 2. Transcription factors (TFs) in mammalian cells Transcription factors are divided into two groups. First, the general TFs (GTFs), including preinitiation complex components TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and THIIH, are the primary protein factors that are required for the initiation of transcription from the TATA box (or TATA element), then elongation is executed by RNA polymerase II (RNA pol II) [1]. The others are the site-specific TFs or the DNA sequence-specific binding proteins. 2.1 The GTFs and TATA-less promoters Molecular mechanisms of the initiation of transcription from TATA box have been well known as the most essential nuclear events in mammalian cells. However, about 70% of mammalian gene promoters have no TATA or TATA-like elements, and they are referred to as TATA-less promoters [2]. In yeast cells, most of genes are regulated by the same general TF-dependent system independent of TATA or TATA-like sequences [3]. TATA-containing and TATA-less promoters

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Section: Accumulation Of Damage From Oxidative Stressessupporting

confidence: 83%

Introductory Chapter: Gene Expression Controlling System and Its Application to Medical Sciences

Uchiumi¹

2019

Gene Expression and Control

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“…Only a few reports are available about this compound. PGB2 is obtained after dehydration of PGE2 [63]. Remarkably, PGB2 enhances the proliferation of Jurkat cells [64].…”

Section: Discussionmentioning

confidence: 99%

Cord Blood Mesenchymal Stem Cells Suppress DC-T Cell Proliferation via Prostaglandin B2

BerkLieke

Jansen

Snowden

et al. 2014

Stem Cells and Development

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Immune suppression is a very stable property of multipotent stromal cells also known as mesenchymal stem cells (MSCs). All cell lines tested showed robust immune suppression not affected by a long culture history. Several mechanisms were described to account for this capability. Since several of the described mechanisms were not causing the immune suppression, the expression pattern of cord-blood-derived MSCs by microarray experiments was determined. Dendritic cells cocultured with cord blood MSCs were compared with cord blood MSCs. Putative immune suppressive candidates were tested to explain this inhibition. We find that cord blood MSCs themselves are hardly immunogenic as tested with allogeneic T-cells. Dendritic cells cocultured with second-party T-cells evoked abundant proliferation that was inhibited by third-party cord blood MSCs. Optimal inhibition was seen with one cord blood MSC for every dendritic cell. Blocking human leukocyte antigen G only saw partial recovery of proliferation. Several cytokines, gangliosides, enzymes like arginase, NO synthase, and indole amine 2,3-dioxygenase as well as the induction of Treg were not involved in the inhibition. The inhibiting moiety was identified as prostaglandin B2 by lipid metabolite analysis of the culture supernatant and confirmed with purified prostaglandin B2.

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“…Whereas NF-E2 was found in erythroid cells, Nrf1 and Nrf2 expression was observed in many tissues ( 90 ). In humans, the Nrf2 gene is located on chromosome 2q31 and in mice on chromosome 2.…”

Section: Nuclear Erythroid-derived 2-related Factormentioning

confidence: 99%

“…The Nrf2 protein consists of 605 amino acids in humans and 597 amino acids in mice ( 90 , 94 ), and is subdivided into six domains, which are evolutionary highly conserved and are termed Nrf2–ECH homology domains, abbreviated Neh1–6. They play important roles in binding to DNA, activation and inactivation of Nrf2.…”

Section: Nuclear Erythroid-derived 2-related Factormentioning

confidence: 99%

“…They play important roles in binding to DNA, activation and inactivation of Nrf2. Protein structure, genetics regulation, and history of discovery of Nrf2 are summarized in the in-depth reviews of Baird and Dinova-Kostova ( 94 ), Ramkissoon et al ( 90 ), and Morita and Motohashi ( 89 ). Baird and Dinova-Kostova discuss several possible activation and regulation mechanisms of Nrf2, i.e., the sequester and release model, which was used in Figure 7 , the “dissociation of Keap1 and Cullin 3 model,” the “hinge and latch model,” the “Keap1 nucleocytoplasmic shuttling model,” and the “ubiquitination of Keap1 model,” as well as some evidence suggesting that Nrf2 directly senses stressors ( 94 ).…”

Section: Nuclear Erythroid-derived 2-related Factormentioning

confidence: 99%

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Transcription Factors in the Cellular Response to Charged Particle Exposure

et al. 2016

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Charged particles, such as carbon ions, bear the promise of a more effective cancer therapy. In human spaceflight, exposure to charged particles represents an important risk factor for chronic and late effects such as cancer. Biological effects elicited by charged particle exposure depend on their characteristics, e.g., on linear energy transfer (LET). For diverse outcomes (cell death, mutation, transformation, and cell-cycle arrest), an LET dependency of the effect size was observed. These outcomes result from activation of a complex network of signaling pathways in the DNA damage response, which result in cell-protective (DNA repair and cell-cycle arrest) or cell-destructive (cell death) reactions. Triggering of these pathways converges among others in the activation of transcription factors, such as p53, nuclear factor κB (NF-κB), activated protein 1 (AP-1), nuclear erythroid-derived 2-related factor 2 (Nrf2), and cAMP responsive element binding protein (CREB). Depending on dose, radiation quality, and tissue, p53 induces apoptosis or cell-cycle arrest. In low LET radiation therapy, p53 mutations are often associated with therapy resistance, while the outcome of carbon ion therapy seems to be independent of the tumor’s p53 status. NF-κB is a central transcription factor in the immune system and exhibits pro-survival effects. Both p53 and NF-κB are activated after ionizing radiation exposure in an ataxia telangiectasia mutated (ATM)-dependent manner. The NF-κB activation was shown to strongly depend on charged particles’ LET, with a maximal activation in the LET range of 90–300 keV/μm. AP-1 controls proliferation, senescence, differentiation, and apoptosis. Nrf2 can induce cellular antioxidant defense systems, CREB might also be involved in survival responses. The extent of activation of these transcription factors by charged particles and their interaction in the cellular radiation response greatly influences the destiny of the irradiated and also neighboring cells in the bystander effect.

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Neurodegeneration from Drugs and Aging‐Derived Free Radicals

Cited by 4 publications

References 710 publications

Introductory Chapter: Gene Expression Controlling System and Its Application to Medical Sciences

Introductory Chapter: Gene Expression Controlling System and Its Application to Medical Sciences

Cord Blood Mesenchymal Stem Cells Suppress DC-T Cell Proliferation via Prostaglandin B2

Transcription Factors in the Cellular Response to Charged Particle Exposure

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