Gene expression of the p16INK4a-Rb and p19Arf-p53-p21Cip/Waf1 signaling pathways in the regulation of hematopoietic stem cell aging by ginsenoside Rg1

Yue, Zhenggang; Jiang, Rong; Wang, Ping; Yan, Bing; Xin, Ying; Li, Feng; Wang, Yaping

doi:10.4238/2014.december.4.3

Cited by 23 publications

(19 citation statements)

References 24 publications

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“…Oxidative stress regulates and promotes the expression of the senescence-associated proteins p19, p53 and p21 ( 28 – 30 ). The activity of the tumor suppressor protein p53 is increased ( 31 ) and p53 induces p21 expression, which has an association with cell cycle arrest triggering cellular senescence ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 ameliorates testicularï¿½senescenceï¿½changes in D‑gal‑induced aging mice via anti‑inflammatory and antioxidative mechanisms

et al. 2018

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With the growing population, aging, extended lifespans and anti-aging have become popular areas of research in the life and social sciences. With increasing age, the structure and function of the testes, the spermatogenetic and androgen-producing organ in the male reproductive system, gradually declines. Ginsenoside Rg1 is an extract of Panax ginseng in traditional Chinese medicine. The extract facilitates anti-aging through its anti-inflammatory and antioxidant properties. However, it has not been reported whether ginsenoside Rg1 delays testicular aging. The present study established D-galactose (D-gal)-induced aging mouse models to examine the protective effects of ginsenoside Rg1 on the structure and function of the testes, and the underlying mechanism. A total of 60 healthy specific pathogen-free male C57BL/6 mice were randomly divided into four groups: Control group; Rg1 group; D-gal + Rg1 group; and D-gal group. The tissues of the mice were used for further experiments. The present study further investigated the effects of Rg1 on the volume of serum testosterone, the testicular index, testicular microscopic structures, the senescence of spermatogenetic cells, the apoptosis of spermatogenetic cells, the activity of the antioxidant enzymes, the levels of inflammatory cytokines, and the levels of S-phase kinase-associated protein (p19), cyclin-dependent kinase inhibitor 1 (p21) and cellular tumor antigen p53 (p53) in D-gal-induced aging mice. In general, compared with the D-gal group, the treatment of Rg1 increased the testis index, serum testosterone level and the active content of superoxide dismutase and the total antioxidant capacity. The percentage of senescence-associated β-galactosidase-positive cells, the level of apoptosis and the volume of methane dicarboxylic aldehyde, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in testicular tissues were significantly decreased, and the expression of p19, p53 and p21 was downregulated due to the treatment with Rg1. The results of the present study demonstrated that ginsenoside Rg1 was able to protect the testes against D-gal-induced aging in mice. In addition, the protective effect of Rg1 may be achieved via antioxidation and downregulation of the p19/p53/p21 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 ameliorates testicularï¿½senescenceï¿½changes in D‑gal‑induced aging mice via anti‑inflammatory and antioxidative mechanisms

et al. 2018

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“…When the p14 N-terminus binds to the C-terminus of Mdm2, the Mdm2 nuclear shuttle is attenuated, and p53 cytoplasmic transport is blocked; thus, Mdm2-mediated p53 proteolysis in the cytoplasm is attenuated [15]. This gradual accumulation of p53 induces the expression of the proapoptotic gene BCL2 associated X (BAX, apoptosis regulator), which is within the WAF1/p21 pathway, and ultimately leads to cell cycle arrest and apoptosis [16,17]. Additionally, p14 competitively binds to CDK4, which inhibits the formation of the CDK4/cyclin D1 complex, resulting in cell cycle arrest in the G1/S phase [18].…”

Section: Introductionmentioning

confidence: 99%

Ara-c induces cell cycle G1/S arrest by inducing upregulation of the INK4 family gene or directly inhibiting the formation of the cell cycle-dependent complex CDK4/cyclin D1

Sun

Tong

et al. 2019

Cell Cycle

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Cytosine arabinoside (Ara-c) is a pyrimidine anti-metabolite that is capable of interfering with cellular proliferation by inhibiting DNA synthesis. Each inhibitor of cyclin-dependent kinase 4 (INK4) family member has the ability to bind to cyclin-dependent kinase 4 (CDK4) and inhibit the formation of the cell cycle-dependent CDK4/cyclin D1 complex, subsequently leading to cell cycle arrest in the G1/S phase. In this study, the expression of INK4 family genes in kidney cancer and the impact of these genes on patient prognosis were examined. Additionally, the effects of INK4 family genes and Ara-c on cell proliferation and tumor formation and development were examined. Finally, a potential association between Ara-c-induced cell cycle arrest and INK4-associated gene expression was evaluated. An upregulation of INK4 family genes was found to be positively correlated with the prognosis of patients with kidney cancer. Both the INK4 family genes and Arac were shown to induce cell cycle arrest and inhibit tumor formation and development. Moreover, Ara-c-induced cell cycle arrest was found to be associated with an Ara-c-induced upregulation of INK4 family gene expression, which ultimately inhibited the formation of the CDK4/cyclin D1 complex. These findings suggested that an upregulation of INK4 family genes has a positive effect on kidney cancer prognosis and can inhibit the formation and development of tumors. Moreover, Ara-c was shown to promote the upregulation of INK4 family genes, at the same time, Ara-c could directly regulate the cell cycle-dependent genes CDK4 and cyclin D1 (CCND1), independent of the INK4 family genes.

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“…Cip1/Waf1 signaling pathways (Yue et al, 2014). Vascular smooth muscle cell (VSMC) senescence plays an important role in the pathogenesis of atherosclerosis (Gorenne et al, 2006).…”

Section: Ink4amentioning

confidence: 99%

Effects of ginsenoside Rg1 on the senescence of vascular smooth muscle cells

Li¹,

Yan²,

Zhang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The development of age-related cardiovascular disease is associated with the senescence of vascular cells. This study aimed to investigate the effect of ginsenoside Rg1 on vascular smooth muscle cell (VSMC) senescence. Primary VSMCs were cultured and divided into control, D-galactose (D-gal), Rg1-L, and Rg1-H groups, which were cultured without and with D-gal, and with low-and highconcentrations of Rg1, respectively. D-gal-induced cellular senescence was identified by b-galactosidase staining, and ultrastructural changes within the cells were observed. The expression of p16, p21, and p53 in the four groups of VSMCs was determined by western blotting, and the cell cycle was investigated by flow cytometry. Compared with the control group, there was an obvious change in the ultrastructure of VSMCs in the D-gal group, and the proportion of b-galactosidasepositive cells was significantly increased (P < 0.05). In addition, p16, p21, and p53 expression was significantly increased (P < 0.05) and the cell cycle was arrested in the G0/G1 phase. Compared with the D-gal group, the percentage of positive cells was significantly reduced (P < 0.05) in the Rg1 groups, the expression of p16, p21, and p53 was significantly reduced (P < 0.05), and the number of cells in the G0/G1 phase decreased (P < 0.05). Ginsenoside Rg1 can inhibit VSMC senescence, and the mechanisms may be related to its partial inhibition of the p16 INK4a /Rb and p53-p21Cip1/Waf1 signaling pathways during the cell cycle.

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Gene expression of the p16INK4a-Rb and p19Arf-p53-p21Cip/Waf1 signaling pathways in the regulation of hematopoietic stem cell aging by ginsenoside Rg1

Cited by 23 publications

References 24 publications

Ginsenoside Rg1 ameliorates testicularï¿½senescenceï¿½changes in D‑gal‑induced aging mice via anti‑inflammatory and antioxidative mechanisms

Ginsenoside Rg1 ameliorates testicularï¿½senescenceï¿½changes in D‑gal‑induced aging mice via anti‑inflammatory and antioxidative mechanisms

Ara-c induces cell cycle G1/S arrest by inducing upregulation of the INK4 family gene or directly inhibiting the formation of the cell cycle-dependent complex CDK4/cyclin D1

Effects of ginsenoside Rg1 on the senescence of vascular smooth muscle cells

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