Apigenin restores impairment of autophagy and downregulation of unfolded protein response regulatory proteins in keratinocytes exposed to ultraviolet B radiation

Li, Li; Li, Min; Xu, Song; Chen, Hongying; Xu, Chen; Gu, Heng

doi:10.1016/j.jphotobiol.2019.03.010

Cited by 24 publications

(12 citation statements)

References 47 publications

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“…It was reported that AP regulate autophagy. For example, AP promoted autophagy through the mTOR/AMPK/ULK1 pathway and could play an antidepressant effect [48], inhibited the growth of cisplatin-resistant colon cancer cells by inducing autophagy and apoptosis [49], and restored impairment of autophagy and downregulation of unfolded protein response regulatory proteins in keratinocytes exposed to ultraviolet B radiation [50]. Studies have suggested that p62 protein is regulated by oxidative stress and is a transcriptional target of Nrf2 [51,52].…”

mentioning

confidence: 99%

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Zhang

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a critical factor in the pathology of age-related macular degeneration (AMD). Apigenin (AP) is a flavonoid with an outstanding antioxidant activity. We had previously observed that AP protected APRE-19 cells against oxidative injury in vitro. However, AP has poor water and fat solubility, which determines its low oral bioavailability. In this study, we prepared the solid dispersion of apigenin (AP-SD). The solubility and dissolution of AP-SD was significantly better than that of the original drug, so the oral bioavailability in rats was better than that of the original drug. Then, the effects of AP-SD on the retina of a model mouse with dry AMD were assessed by fundus autofluorescence (FAF), optical coherence tomography (OCT), and electron microscopy; the results revealed that AP-SD alleviated retinopathy. Further research found that AP-SD promoted the nuclear translocation of Nrf2 and increased expression levels of the Nrf2 and target genes HO-1 and NQO-1. AP-SD enhanced the activities of SOD and GSH-Px and decreased the levels of ROS and MDA. Furthermore, AP-SD upregulated the expressions of p62 and LC3II in an Nrf2-dependent manner. However, these effects of AP-SD were observed only in the retina of Nrf2 WT mice, not in Nrf2 KO mice. In addition, the therapeutic effect of AP-SD was dose dependent, and AP did not work. In conclusion, AP-SD significantly enhanced the bioavailability of the original drug and reduced retinal oxidative injury in the model mouse of dry AMD in vivo. The results of the underlying mechanism showed that AP-SD upregulated the expression of antioxidant enzymes through the Nrf2 pathway and upregulated autophagy, thus inhibiting retinal oxidative damage. AP-SD may be a potential compound for the treatment of dry AMD.

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confidence: 99%

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Zhang

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…In addition, quercetrin-the common flavonoid could reduce ROS generation in skin keratinocyte cells and restore CAT activity, further to inhibit UVB-induced cutaneous damage and apoptosis in vitro and in vivo, thereby verifying that quercitrin plays a photoprotective role in UVB-induced oxidative damage to skin [96,97]. Apigenin, in the same way, availably protects keratinocytes against UVB-induced damage by restoring autophagy, inhibiting apoptosis/cell death and up-regulating DNA-damage response proteins, suggesting apigenin as a promising application in skin photodamage [98]. It was discovered that fisetin, a kind of flavonol existing in fruits and vegetables, has a favourable photoprotection against UVB-induced damage to skin fibroblasts and dermal collagen through decreasing intracellular ROS and NO production via mediating in multiple signaling pathways including MAPKs, NF-κB and PI3K/Akt [99].…”

Section: Flavonoids In Skin Photodamagementioning

confidence: 81%

Current evidence to support the therapeutic potential of flavonoids in oxidative stress-related dermatoses

Xian

Guo

et al. 2021

Redox Report

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Background: Skin, as a crucial external defense organ, is more vulnerable to oxidative stress (OS) insult, reactive oxygen species (ROS)-mediated OS in particular. OS results from a redox imbalance caused by various extrinsic stimuli and occurs once the oxidants production overwhelming the antioxidants capacity, through mediating in DNA damage, lipid peroxidation (LPO), protein oxidation and a serial of signaling pathways activation/inactivation, thereby offering favorable conditions for the occurrence and development of numerous diseases especially some dermatoses, e.g. psoriasis, vitiligo, skin photodamage, skin cancer, systemic sclerosis (SSc), chloasma, atopic dermatitis (AD), pemphigus, etc. Targeting OS molecular mechanism, a variety of anti-OS agents emerge, in which flavonoids, natural plant extracts, stand out. Objectives: To discuss the possible mechanisms of OS mediating in dermatoses and summarize the properties of flavonoids as well as their applications in OS-related skin disorders. Methods: Published papers on flavonoids and OS-related skin diseases were collected and reviewed via database searching on PubMed, MEDLINE and Embase, etc. Results: It has been confirmed that flavonoids, belonging to polyphenols, are a class of plant secondary metabolites widely distributed in various plants and possess diverse bioactivities especially their potent antioxidant capacity. Moreover, flavonoids benefit to suppress OS via eliminating free radicals and mediating the corresponding signals, further excellently working in the prevention and management of OS-related skin diseases. Conclusion: Flavonoids have the potential therapeutic effects on oxidative stress-related dermatoses. However, more studies on specific mechanism as well as the dosage of flavonoids are needed in future.

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“…HaCaT (a cell line of non-tumorigenic human keratinocytes) and A431 (a cell line of cSCC) were cultured in Dulbecco's Modified Eagle's Medium (Gibco, 11965-092) supplemented with 10% fetal bovine serum. HEKs were obtained from neonatal foreskin as described previously [ 17 ] and cultured in defined keratinocyte serum free media (Gibco, 10785-012). All cells were maintained in a humidified atmosphere of 5% CO 2 at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Trehalose Protects Keratinocytes against Ultraviolet B Radiation by Activating Autophagy via Regulating TIMP3 and ATG9A

Li¹,

Chen²,

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Trehalose, a natural disaccharide, is synthesized by many organisms when cells are exposed to stressful stimuli. On the basis of its ability to modulate autophagy, trehalose has been considered an innovative drug for ameliorating many diseases, but its molecular mechanism is not well described. Previous findings demonstrated that trehalose plays a photoprotective role against ultraviolet (UV) B-induced damage through autophagy induction in keratinocytes. In this study, coimmunoprecipitation, label-free quantitative proteomic and parallel reaction monitoring, and western blot analysis demonstrated that trehalose promotes the interaction between tissue inhibitor of metalloproteinase (TIMP) 3 and Beclin1. Western blot and immunofluorescence staining analysis suggested that trehalose increases ATG9A localization in lysosomes and decreases its localization in the endoplasmic reticulum. Furthermore, in the presence or absence of UVB radiation, we evaluated the influence of TIMP3 and ATG9A small interfering RNA (siRNA) on the effect of trehalose on autophagy, cell death, migration, or interleukin-8 expression in keratinocytes, including HaCaT, A431, and human epidermal keratinocytes. The results revealed that in HaCaT cells, TIMP3 and ATG9A siRNA resulted in attenuation of trehalose-induced autophagy and inhibited cell death. In A431 cells, TIMP3 and ATG9A siRNA led to attenuation of trehalose-induced autophagy and cell death and inhibited migration. In human epidermal keratinocytes, trehalose-induced autophagy and inhibition of the interleukin-8 expression were blocked by ATG9A but not TIMP3 siRNA. In addition, the results of quantitative real-time PCR and immunohistochemistry analysis demonstrated the abnormal expression of TIMP3 and ATG9A in actinic keratosis and cutaneous squamous cell carcinoma skin tissues. These findings suggest the protective effects of trehalose in normal keratinocytes and its inhibitory effects on cancerous keratinocytes, possibly mediated by activation of autophagy and regulation of TIMP3 and ATG9A, providing the mechanistic basis for the potential use of trehalose in the prevention or treatment of UVB-induced skin diseases.

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Apigenin restores impairment of autophagy and downregulation of unfolded protein response regulatory proteins in keratinocytes exposed to ultraviolet B radiation

Cited by 24 publications

References 47 publications

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy

Current evidence to support the therapeutic potential of flavonoids in oxidative stress-related dermatoses

Trehalose Protects Keratinocytes against Ultraviolet B Radiation by Activating Autophagy via Regulating TIMP3 and ATG9A

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