Icariin delays homocysteine-induced endothelial cellular senescence involving activation of the PI3K/AKT-eNOS signaling pathway

Duan, Xiaohong; Xu, Chao; Huang, Jianhua; Zhou, Wei; Sun, Bing

doi:10.3109/13880209.2012.738332

Cited by 38 publications

(15 citation statements)

References 35 publications

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“…Notably, SLC30A10 and SLC30A5 are both under the control of ZNF658 (Ogo et al, 2015) and the ZNF658 to SLC30A10 mRNA ratio was highly correlated with the mRNA of the senescence marker p16, suggesting that the component of the Zn-homeostatic machinery regulated by ZNF658 may be particularly pivotal in the transition between endothelial cell replication and senescence. In concordance with this proposal, the Zn transcriptional regulatory element (ZTRE), which mediates the effect of ZNF658 on gene transcription, was identified in at least 3 genes (HSPA9, RAD51 and NOS3) (Coneyworth et al, 2012) that are known to counteract cellular senescence (Rodier et al, 2011;Xiao-Hong et al, 2013;Yaguchi et al, 2007).…”

Section: Discussionmentioning

confidence: 56%

Changes in Zn homeostasis during long term culture of primary endothelial cells and effects of Zn on endothelial cell senescence

Malavolta

Costarelli

Giacconi

et al. 2017

Experimental Gerontology

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Endothelial cell senescence and Zn nutritional status influence cardiovascular disease. The influence of Zn appears dichotomous, hence it is imperative to understand the relationship with cellular senescence to improve knowledge about the molecular and cellular basis of the disease. Here we aimed to determine: 1) the impact of chronic exposure to a moderately high dose of Zn on senescence of endothelial cells; 2) the changes in Zn homeostasis during the lifespan of primary cultured endothelial cells; and 3) the susceptibility of proliferating and senescent endothelial cells to cell death after short term exposure to increasing doses of Zn and of the Zn chelator TPEN. Chronic exposure to Zn accelerated senescence and untreated cells at later passages, where doubling time had increased, displayed relocation of labile Zn and altered expression of genes involved in the response to Zn toxicity, including SLC30A1, SLC39A6, SLC30A5, SLC30A10 and metallothioneins, indicating that senescent cells have altered zinc homeostasis. Most Zn-dependent genes that were expressed differently between early and late passages were correlated with changes in the expression of anti-apoptotic genes. Short-term treatment with a high dose of Zn leads to cell death, but only in the population of cells at both earlier and later passages that had already entered senescence. In contrast, Zn depletion led to death of cells at earlier but not later passages, which suggests that there are sub-populations of senescent cells that are resistant to Zn depletion. This resistant senescent cell population may accumulate under conditions of Zn deficiency and contribute to vascular pathology.

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Section: Discussionmentioning

confidence: 56%

Changes in Zn homeostasis during long term culture of primary endothelial cells and effects of Zn on endothelial cell senescence

Malavolta

Costarelli

Giacconi

et al. 2017

Experimental Gerontology

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“…[4] ing the PI3K/Akt/eNOS-dependent signaling pathway [118]. and position might be an influence factor [112].…”

Section: Umr106 Cellsmentioning

confidence: 99%

“…Icariin demonstrated higher effica-115 cy than genistein to promote osteogenic differentiation and maturation 116 of osteoblast, which might be due to the C-8 prenyl group [71,74]. 117 Icariin, curculigoside and berberine, the bioactive constituents in Er- 118 Xian Decoction, synergistically decrease formation of bone resorption 119 pits and the activity of TRAP [129]. Icariin might produce cooperative ac-120 tion with trace metal elements on the proliferation and differentiation 121 of osteoblasts [145].…”

mentioning

confidence: 99%

Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii

et al. 2015

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“…In agreement with this finding, another study congruently shows that androgen receptor (AR), PI3K/Akt, and ERK pathway are involved in increased release of NO via eNOS activation ( Koizumi et al, 2010 ). Also, through the Akt/eNOS/NO pathway, Icariin prevents endothelial senescence induced by homocyteine both in vitro and in vivo ( Xiao-Hong et al, 2013 ) as well as s -nitrosogultathione induced endothelial apoptosis ( Huang et al, 2016 ). In addition to the upregulation of eNOS phosphorylation at Ser1177, Icariin also increases eNOS mRNA and protein expression, suggesting Icariin could also regulate eNOS level at the transcriptional and translational level ( Xu and Huang, 2007 ).…”

Section: Anti-atherosclerotic Effects Of Icariinmentioning

confidence: 99%

Icariin, an Anti-atherosclerotic Drug from Chinese Medicinal Herb Horny Goat Weed

Fang

Zhang

2017

Front. Pharmacol.

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Icariin is a major bioactive pharmaceutical constituent isolated from Chinese medicine Horny Goat Weed (Ying Yang Huo) with potent cardiovascular protective functions. Emerging evidence in the past decade has shown that Icariin possesses multiple atheroprotective functions, through multiple mechanisms, including attenuating DNA damage, correcting endothelial dysfunction, inhibiting the proliferation and migration of smooth muscle cells, repressing macrophage-derived foam cell formation and inflammatory responses, as well as preventing platelet activation. All of these protective effects, combined with its lipid-modulatory effects, contribute to the broad atheroprotective effects of Icariin. In this review, we will summarize the anti-atherosclerotic properties of Icariin and highlight future perspectives in developing Icariin as a promising anti-atherosclerotic drug.

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Icariin delays homocysteine-induced endothelial cellular senescence involving activation of the PI3K/AKT-eNOS signaling pathway

Cited by 38 publications

References 35 publications

Changes in Zn homeostasis during long term culture of primary endothelial cells and effects of Zn on endothelial cell senescence

Changes in Zn homeostasis during long term culture of primary endothelial cells and effects of Zn on endothelial cell senescence

Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii

Icariin, an Anti-atherosclerotic Drug from Chinese Medicinal Herb Horny Goat Weed

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