The role of SIRT1/AKT/ERK pathway in ultraviolet B induced damage on human retinal pigment epithelial cells

Chou, Wen Wen; Chen, Ku Chung; Wang, Yung Song; Wang, Jaw‐Yuan; Liang, Chung Ling; Juo, Suh Hang Hank

doi:10.1016/j.tiv.2013.05.002

Cited by 35 publications

(32 citation statements)

References 49 publications

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“…In addition, SirT1 was previously reported to exert significant protective effects against ocular diseases in animal models, including cataracts, retinal degeneration, optic neuritis and uveitis (38). Regarding the protective roles of SirT1 in RPEs, it has been demonstrated that SirTl may be a significant regulator in the protection of RPEs against ultraviolet B-induced injury, and may abrogate amyloid-β-induced inflammation (39,40). In the present study, SirT1 was demonstrated to significantly attenuate the effects induced by oxidants.…”

Section: A B C Dsupporting

confidence: 57%

SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress

Wei

Zhang

et al. 2015

Molecular Medicine Reports

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Abstract.It has been previously demonstrated that there are interactions between sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3), which have versatile roles in various microenvironments. However, whether or not there is crosstalk between these two molecules during oxidative stress, and what mechanism of crosstalk occurs in retinal pigmented epithelium cells (RPEs), the protection of which may delay the process of age-related macular degeneration (AMD), has required further elucidation. The present study aimed to investigate the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative stress. The rates of proliferation and apoptosis, levels of intracellular reactive oxygen species and cell senescence of RPEs, induced by oxidants [H 2 O 2 and oxidized low density lipoprotein (oxLDL)], were evaluated. The results revealed a downregulation of SirT1 expression, and an upregulation of STAT3 expression during oxidative stress. Further investigation indicated that SirT1 protected RPEs from oxidative stress-induced damage. Furthermore, gain-and loss-of-function experiments indicated that SirT1 had negative effects on the regulation of STAT3 expression in RPEs during oxidative stress. Notably, STAT3 directly protected the cells from oxidative stress, rather than depending on SirT1. Additionally, the protective effects of STAT3 had no association with the modulation of cell senescence during oxidative stress. In conclusion, SirT1 had negative effects on the regulation of STAT3 expression during oxidative stress. However, SirT1 and STAT3 demonstrated protective roles against oxidative stress in RPEs. These results therefore suggested that there was an equilibrium mechanism between SirT1 and STAT3 against oxidative stress, meaning that an equilibrium mechanism is required to be considered when combined application of STAT3 and SirT1 were performed to treat AMD.

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Section: A B C Dsupporting

confidence: 57%

SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress

Wei

Zhang

et al. 2015

Molecular Medicine Reports

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“…SIRT1 is an NAD-dependent histone deacetylase that is known to be increased by heat stress [18, 19], but inhibited by UVB [20]. Its activity is vital for the maintenance of chromosomal integrity and control of various cellular processes including cell metabolism and cellular stress response [21, 22].…”

Section: Introductionmentioning

confidence: 99%

SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes

Calapre

Gray

Kurdykowski³

et al. 2017

BMC Dermatol

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BackgroundExposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes.ResultsActivation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin.ConclusionThis study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heatElectronic supplementary materialThe online version of this article (doi:10.1186/s12895-017-0060-y) contains supplementary material, which is available to authorized users.

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“…Moreover, accumulating evidence indicates that p53 play an important role in UVB-induced DNA damage in Human HaCaT Keratinocytes cells [24]. And UVB dose-dependently suppressed the growth of RPE cells by activating the phosphatidylinositol 3-kinase (PI3K) pathway [25]. Considering UV irradiation in corneal epithelium, Pifithrin- α could inhibit p53 and decrease damaged cells and apoptosis [26].…”

Section: Discussionmentioning

confidence: 99%

PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

Long

Huang

et al. 2017

BioMed Research International

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Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α (one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.

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The role of SIRT1/AKT/ERK pathway in ultraviolet B induced damage on human retinal pigment epithelial cells

Cited by 35 publications

References 49 publications

SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress

SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative stress

SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes

PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

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