Corrigendum to “Glucose Oxidase Induces Cellular Senescence in Immortal Renal Cells through ILK by DownregulatingKlothoGene Expression”

Glucose Oxidase Induces Cellular Senescence in Immortal Renal Cells through ILK by DownregulatingKlothoGene Expression

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/416738 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Nuria Troyano-Suárez ◽

María del Nogal-Avila ◽

Inés Mora ◽

Patricia Sosa ◽

Susana López-Ongil ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Protein Expression ◽

Glucose Oxidase ◽

Cellular Senescence ◽

Renal Cells ◽

Long Time ◽

P16 Expression ◽

Expression And Activity ◽

In Cells

Cellular senescence can be prematurely induced by oxidative stress involved in aging. In this work, we were searching for novel intermediaries in oxidative stress-induced senescence, focusing our interest on integrin-linked kinase (ILK), a scaffold protein at cell-extracellular matrix (ECM) adhesion sites, and on theKlothogene. Cultured renal cells were treated with glucose oxidase (GOx) for long time periods. GOx induced senescence, increasing senescence associatedβ-galactosidase activity and the expression of p16. In parallel, GOx increased ILK protein expression and activity. Ectopic overexpression of ILK in cells increased p16 expression, even in the absence of GOx, whereas downregulation of ILK inhibited the increase in p16 due to oxidative stress. Additionally, GOx reducedKlothogene expression and cells overexpressing Klotho protein did not undergo senescence after GOx addition. We demonstrated a direct link between ILK andKlothosince silencing ILK expression in cells and mice increasesKlothoexpression and reduces p53 and p16 expression in renal cortex. In conclusion, oxidative stress induces cellular senescence in kidney cells by increasing ILK protein expression and activity, which in turn reducesKlothoexpression. We hereby present ILK as a novel downregulator ofKlothogene expression.

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Lamin B receptor: role on chromatin structure, cellular senescence and possibly aging

Biochemical Journal ◽

10.1042/bcj20200165 ◽

2020 ◽

Vol 477 (14) ◽

pp. 2715-2720

Author(s):

Susana Castro-Obregón

Keyword(s):

Cellular Senescence ◽

Nuclear Membrane ◽

Chromatin Structure ◽

Cholesterol Synthesis ◽

Reductase Activity ◽

Chimeric Protein ◽

Nuclear Lamina ◽

Lamin B ◽

Inner Nuclear Membrane ◽

Lamin B Receptor

The nuclear envelope is composed by an outer nuclear membrane and an inner nuclear membrane, which is underlain by the nuclear lamina that provides the nucleus with mechanical strength for maintaining structure and regulates chromatin organization for modulating gene expression and silencing. A layer of heterochromatin is beneath the nuclear lamina, attached by inner nuclear membrane integral proteins such as Lamin B receptor (LBR). LBR is a chimeric protein, having also a sterol reductase activity with which it contributes to cholesterol synthesis. Lukasova et al. showed that when DNA is damaged by ɣ-radiation in cancer cells, LBR is lost causing chromatin structure changes and promoting cellular senescence. Cellular senescence is characterized by terminal cell cycle arrest and the expression and secretion of various growth factors, cytokines, metalloproteinases, etc., collectively known as senescence-associated secretory phenotype (SASP) that cause chronic inflammation and tumor progression when they persist in the tissue. Therefore, it is fundamental to understand the molecular basis for senescence establishment, maintenance and the regulation of SASP. The work of Lukasova et al. contributed to our understanding of cellular senescence establishment and provided the basis that lead to the further discovery that chromatin changes caused by LBR reduction induce an up-regulated expression of SASP factors. LBR dysfunction has relevance in several diseases and possibly in physiological aging. The potential bifunctional role of LBR on cellular senescence establishment, namely its role in chromatin structure together with its enzymatic activity contributing to cholesterol synthesis, provide a new target to develop potential anti-aging therapies.

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