Limitations to adaptive homeostasis in an hyperoxia-induced model of accelerated ageing

Pomatto, Laura C.D.; Sun, Patrick Y.; Yu, Kelsi; Gullapalli, Sandhyarani; Bwiza, Conscience P.; Sisliyan, Christina; Wong, Shirley; Zhang, Hongqiao; Oliver, Peter L.; Davies, Kay E.; Davies, Kelvin J.A.

doi:10.1016/j.redox.2019.101194

Cited by 18 publications

(12 citation statements)

References 78 publications

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“…Thus, Bach1 plays an important role in the redox induction of HO-1 and NQO1 [ 157 , 161 ]. Recently, Pomatto and colleagues demonstrated in vitro that hyperoxia strongly elevates Bach1 levels and the competitive effect of Bach1 and Nrf2 increases in a time-dependent manner [ 162 ]. Additionally, silencing Bach1 increases basal expression of Nrf2-regulated antioxidant genes in both the young and older human bronchial epithelial cells [ 163 ], suggesting that Bach1 is a potential target for antiaging intervention.…”

Section: Bach1 and C - Mycmentioning

confidence: 99%

“…Davies and Forman have proposed that although Bach1 and c - Myc expression increased with age, continual adaptive homeostasis contributes to lower cancer risk [ 171 ]. Additionally, Pomatto et al believe that changes in the balance of Nrf2 , Bach1 , and c - Myc levels may be the cause of serious disturbances to the stress response and adaptive homeostasis during chronic hyperoxia and aging [ 162 ]. Nevertheless, research has mainly focused on quantitative changes when examining the interaction between the two inhibitors, Nrf2, and aging.…”

Section: Bach1 and C - Mycmentioning

confidence: 99%

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The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging

Chao

Xiao

2021

Oxidative Medicine and Cellular Longevity

190

136

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Oxidative stress, a term that describes the imbalance between oxidants and antioxidants, leads to the disruption of redox signals and causes molecular damage. Increased oxidative stress from diverse sources has been implicated in most senescence-related diseases and in aging itself. The Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor-erythroid 2-related factor 2 (Nrf2) system can be used to monitor oxidative stress; Keap1-Nrf2 is closely associated with aging and controls the transcription of multiple antioxidant enzymes. Simultaneously, Keap1-Nrf2 signaling is also modulated by a more complex regulatory network, including phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), protein kinase C, and mitogen-activated protein kinase. This review presents more information on aging-related molecular mechanisms involving Keap1-Nrf2. Furthermore, we highlight several major signals involved in Nrf2 unbinding from Keap1, including cysteine modification of Keap1 and phosphorylation of Nrf2, PI3K/Akt/glycogen synthase kinase 3β, sequestosome 1, Bach1, and c-Myc. Additionally, we discuss the direct interaction between Keap1-Nrf2 and the mammalian target of rapamycin pathway. In summary, we focus on recent progress in research on the Keap1-Nrf2 system involving oxidative stress and aging, providing an empirical basis for the development of antiaging drugs.

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Section: Bach1 and C - Mycmentioning

confidence: 99%

Section: Bach1 and C - Mycmentioning

confidence: 99%

The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging

Chao

Xiao

2021

Oxidative Medicine and Cellular Longevity

190

136

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“…infection since the action of ROS is nonspecific and causes damage to the surrounding host cells, consequently leading to inflammation and tissue injury (Morgado et al, 2018;Herb and Schramm, 2021). Therefore, in the presence of pro-oxidant molecules, such as • O − 2 , adaptive homeostasis mechanisms must be activated as a way to protect against tissue damage (Pomatto et al, 2019). Despite producing • O − 2 in a more pronounced manner, mice of the C57BL/6 strain showed higher collagen deposition, suggesting an ability to balance pro-and antioxidant properties, thus explaining the concomitant elimination of the parasite combined with the tissue protection capacity found in C57BL/6 mice (Morgado et al, 2018).…”

Section: The Macrophages Recruited To the Lesion Site Are Important For The Evolution Of Edema And In The Arginase-1 Presencementioning

confidence: 99%

Murine Susceptibility to Leishmania amazonensis Infection Is Influenced by Arginase-1 and Macrophages at the Lesion Site

Tomiotto-Pellissier

Miranda-Sapla

Silva

et al. 2021

Front. Cell. Infect. Microbiol.

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Cutaneous leishmaniasis is a zoonotic infectious disease broadly distributed worldwide, causing a range of diseases with clinical outcomes ranging from self-healing infections to chronic disfiguring disease. The effective immune response to this infection is yet to be more comprehensively understood and is fundamental for developing drugs and vaccines. Thus, we used experimental models of susceptibility (BALB/c) and partial resistance (C57BL/6) to Leishmania amazonensis infection to investigate the local profile of mediators involved in the development of cutaneous leishmaniasis. We found worse disease outcome in BALB/c mice than in C57BL/6 mice, with almost 15 times higher parasitic load, ulcerated lesion formation, and higher levels of IL-6 in infected paws. In contrast, C57BL/6 presented higher levels of IFN-γ and superoxide anion (•O2−) after 11 weeks of infection and no lesion ulcerations. A peak of local macrophages appeared after 24 h of infection in both of the studied mice strains, followed by another increase after 240 h, detected only in C57BL/6 mice. Regarding M1 and M2 macrophage phenotype markers [iNOS, MHC-II, CD206, and arginase-1 (Arg-1)], we found a pronounced increase in Arg-1 levels in BALB/c after 11 weeks of infection, whereas C57BL/6 showed an initial predomination of markers from both profiles, followed by an M2 predominance, coinciding with the second peak of macrophage infiltration, 240 h after the infection. Greater deposition of type III collagen and lesion resolution was also observed in C57BL/6 mice. The adoptive transfer of macrophages from C57BL/6 to infected BALB/c at the 11th week showed a reduction in both edema and the number of parasites at the lesion site, in addition to lower levels of Arg-1. Thus, C57BL/6 mice have a more effective response against L. amazonensis, based on a balance between inflammation and tissue repair, while BALB/c mice have an excessive Arg-1 production at late infection. The worst evolution seems to be influenced by recruitment of Arg-1 related macrophages, since the adoptive transfer of macrophages from C57BL/6 mice to BALB/c resulted in better outcomes, with lower levels of Arg-1.

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“…(H) Chromatin immunoprecipitation (ChIP)-polymerase chain reaction (qPCR) analysis validates the enrichment of BACH1 at the enhancer of CDKN1A gene (n 3 independent experiments, data are mean ± SEM, unpaired 2-tailed t-test, *p < 0.05). (Pomatto et al, 2019). Our recent study showed that BACH1 recruited an essential pluripotency regulator NANOG and the MLL/SET1 complexes to maintain the activity of promoters and (super-) enhancers in embryonic stem cells (Niu et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging

Pan

Qin

et al. 2021

Front. Cell Dev. Biol.

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Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged cardiac vasculature in monkey and mouse and 2) demonstrate the role of transcription factor BACH1 in the regulation of endothelial cell (EC) senescence and its mechanisms. Here we analyzed published single-cell RNA sequencing (scRNA-seq) data from monkey coronary arteries and aortic arches and mouse hearts. We revealed that the gene expression of YAP1, insulin receptor, and VEGF receptor 2 was downregulated in both aged ECs of coronary arteries’ of monkey and aged cardiac capillary ECs of mouse, and proliferation-related cardiac capillary ECs were significantly decreased in aged mouse. Increased interaction of ECs and immunocytes was observed in aged vasculature of both monkey and mouse. Gene regulatory network analysis identified BACH1 as a master regulator of aging-related genes in both coronary and aorta ECs of monkey and cardiac ECs of mouse. The expression of BACH1 was upregulated in aged cardiac ECs and aortas of mouse. BACH1 aggravated endothelial cell senescence under oxidative stress. Mechanistically, BACH1 occupied at regions of open chromatin and bound to CDKN1A (encoding for P21) gene enhancers, activating its transcription in senescent human umbilical vein endothelial cells (HUVECs). Thus, these findings demonstrate that BACH1 plays an important role in endothelial cell senescence and vascular aging.

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Limitations to adaptive homeostasis in an hyperoxia-induced model of accelerated ageing

Cited by 18 publications

References 78 publications

The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging

The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging

Murine Susceptibility to Leishmania amazonensis Infection Is Influenced by Arginase-1 and Macrophages at the Lesion Site

Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging

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