Cellular senescence and aging: the role of B-MYB

Mowla, Sophia; Lam, Eric W.‐F.; Jat, Parmjit

doi:10.1111/acel.12242

Cited by 73 publications

(61 citation statements)

References 69 publications

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“…Hence, we investigated the impact of HG on SA‐β‐Gal activity in HT‐22 cells and it was found that HG‐treated HT‐22 cells display obviously increased the percentage of SA‐β‐Gal positive cells. In addition, cellular senescence is also associated with increased expressions of senescence biomarker p16 INK4a and p21 CIP1 . Therefore, the effects of HG on the expression levels of p16 INK4a and p21 CIP1 in HT‐22 cells were detected and we demonstrated that HG upregulated the expression levels of p16 INK4a and p21 CIP1 in HT‐22 cells.…”

Section: Discussionmentioning

confidence: 73%

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Zhu

Fan

Tang

et al. 2018

Clin Exp Pharma Physio

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Hyperglycaemia-induced neurotoxicity involved in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglyceamic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti-aging function in many tissues. However, the role of Spd in hyperglyceamia-induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)-treated HT-22 cell as vitro model to investigate whether Spd protects neurons against hyperglyceamia-induced senescence and the mediatory role of CB1 receptor. The HT-22 cells were cultured in HG condition in the presence of different dose of Spd. Then, the viability of cells was measured by Cell Counting Kit-8 (CCK-8) assay. The senescence of cells was detected by Senescence-associated β-galactosidase (SA-β-Gal) staining. The expressions of p16 , p21 and CB1 receptor were measured by western blot. We found that Spd inhibited HG-induced neurotoxicity (the loss of cell viability) and senescence (the increase of SA-β-Gal positive cells, the upregulation of p16 and p21 ) in HT-22 cells. Also, Spd prevented HG-induced downregulation of CB1 receptor in HT-22 cells. Furthermore, we demonstrated that AM251 (a specific inhibitor of the CB1 receptor) reversed the protective effects of Spd on HG-induced neurotoxicity and senescence. These results indicated that Spd prevents HG-induced neurotoxicity and senescence via the upregulation of CB1 receptor. Our findings provide a promising future of Spd-based preventions and therapies for diabetic encephalopathy.

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Section: Discussionmentioning

confidence: 73%

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Zhu

Fan

Tang

et al. 2018

Clin Exp Pharma Physio

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“…A global gene expression analysis of different cancer types found FOXM1, E2F1, and MYBL2 are disproportionately upregulated in p53 mutant cancers [22]. MYB-related protein B (B-MYB/MYBL2) coordinates cell cycle transition in conjunction with multivulval class B (MuvB) complex and FOXM1[23]. The binding of FoxM1 to the promoters of genes involved in G2/M is dependent on the transcription factor B-Myb [24].…”

Section: Foxm1 and The Cell Cyclementioning

confidence: 99%

FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways

Kelleher

O’Sullivan

2016

Oncotarget

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FOXM1 is a pro-proliferative transcription factor that promotes cell cycle progression at the G1-S, and G2-M transitions. It is activated by phosphorylation usually mediated by successive cyclin – cyclin dependent kinase complexes, and is highly expressed in sarcoma. p53 down regulates FOXM1 and FOXM1 inhibition is also partly dependent on Rb and p21. Abnormalities of p53 or Rb are frequent in sporadic sarcomas with bone or soft tissue sarcoma, accounting for 36% of index cancers in the high penetrance TP53 germline disorder, Li-Fraumeni syndrome.FOXM1 stimulates transcription of pluripotency related genes including SOX2, KLF4, OCT4, and NANOG many of which are important in sarcoma, a disorder of mesenchymal stem cell/ partially committed progenitor cells. In a selected specific, SOX2 is uniformly expressed in synovial sarcoma. Embryonic pathways preferentially used in stem cell such as Hippo, Hedgehog, and Wnt dominate in FOXM1 stoichiometry to alter rates of FOXM1 production or degradation. In undifferentiated pleomorphic sarcoma, liposarcoma, and fibrosarcoma, dysregulation of the Hippo pathway increases expression of the effector co-transcriptional activator Yes-Associated Protein (YAP). A complex involving YAP and the transcription factor TEAD elevates FOXM1 in these sarcoma subtypes. In another scenario 80% of desmoid tumors have nuclear localization of β-catenin, the Wnt pathway effector molecule. Thiazole antibiotics inhibit FOXM1 and because they have an auto-regulator loop FOXM1 expression is also inhibited. Current systemic treatment of sarcoma is of limited efficacy and inhibiting FOXM1 represents a potential new strategy.

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“…While transcription factors YY1 and Id1 suppress p16 INK4A expression, transcription factors CTCF, Sp1, and Ets family members activate p16 INK4A transcription. Senescence occurs with the inactivation of suppressor elements leading to the enhanced expression of p16 INK4A . Once the cell cycle is arrested, DNA repair mechanism would be activated, and with successful repair eventually recovery from checkpoint may occur .…”

Section: Cin Can Damage Dna and Is Mutagenic On Cellular Levelmentioning

confidence: 99%

Emerging links among Chromosome Instability (CIN), cancer, and aging

Rao

Asch

Yamada

2016

Molecular Carcinogenesis

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Aneuploidy was predicted to cause cancer. To test the prediction, various Chromosome Instability (CIN) mice models that carry transgenic mutations in mitotic regulators have been created. The availability of these mice has aided researchers in discovering connections between CIN, cancer, and aging. This review will focus on recent interdisciplinary findings regarding how CIN and aneuploidy affect carcinogenesis, immune dysfunction, and aging. High CIN can be generated in vivo by various intrinsic alterations (e.g., gene mutation, epigenetic modification) and extrinsic/environmental challenges (e.g., biological, chemical, biophysical), while immune surveillance, cell death, and natural turnover can remove cells with CIN. CIN itself is mutagenic and may cause further cellular mutations, which can be carcinogenic. Mitotically damaged cells can activate senescence-related tumor suppressors (e.g., p21 , p27 , p16 ), which may lead to tissue-level senescence/aging through inflammatory paracrine mechanisms called Senescence-Associated Secretory Phenotype (SASP) and Senescence Inflammatory Response (SIR). Organs with high CIN show altered gene expressions in both organ-specific and non-specific manners. Organ-specific gene expression signatures include activation of oncogenic pathways. Non-organ-specific gene expression signatures include metabolic changes and downregulations in immune functions. Immune surveillance normally targets senescent cells and tetraploid cells, a form of aneuploidy, for elimination. However, with partial immune dysfunction, immune surveillance is weakened with systemic CIN. In this case, more senescent cells and aneuploid cells survive, which further leads to an inflammatory, pro-tumorigenic, and senescent/aging microenvironment. We also discuss how we may intervene in this sequence of events to prevent CIN- or age-related carcinogenesis and/or some aspects of tissue aging. © 2016 Wiley Periodicals, Inc.

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Cellular senescence and aging: the role of B-MYB

Cited by 73 publications

References 69 publications

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways

Emerging links among Chromosome Instability (CIN), cancer, and aging

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