دورية أكاديمية
أعرض في EDS

KTN1 mediated unfolded protein response protects keratinocytes from ionizing radiation-induced DNA damage.

التفاصيل البيبلوغرافية
العنوان: KTN1 mediated unfolded protein response protects keratinocytes from ionizing radiation-induced DNA damage.
المؤلفون: Niu X; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, China., Shen Y; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, China., Wen Y; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, China., Mi X; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, China., Xie J; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, China., Zhang Y; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, China., Ding Z; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, China. Electronic address: dingzh@smu.edu.cn.
المصدر: Journal of dermatological science [J Dermatol Sci] 2024 Apr; Vol. 114 (1), pp. 24-33. Date of Electronic Publication: 2024 Feb 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9011485 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-569X (Electronic) Linking ISSN: 09231811 NLM ISO Abbreviation: J Dermatol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier, c1990-
مواضيع طبية MeSH: Cell Proliferation*/radiation effects , Cell Proliferation*/drug effects , DNA Damage*/radiation effects , HaCaT Cells* , Keratinocytes*/radiation effects , Keratinocytes*/metabolism , Radiation, Ionizing* , Unfolded Protein Response*/radiation effects , Unfolded Protein Response*/drug effects, Humans ; Cell Line ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/radiation effects ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum Stress/radiation effects ; Endoplasmic Reticulum Stress/drug effects ; Membrane Proteins/metabolism ; Membrane Proteins/genetics ; Skin/radiation effects ; Skin/pathology ; Skin/cytology ; Skin/drug effects ; Skin/metabolism
مستخلص: Background: The unfolded protein response (UPR) is one of the cytoprotective mechanisms against various stresses and essential for the normal function of skin. Skin injury caused by ionizing radiation (IR) is a common side effect of radiotherapy and it is unclear how UPR affects IR-induced skin injury.
Objectives: To verify the effect of UPR on IR-induced DNA damage in keratinocytes and the relation between an endoplasmic reticulum (ER) protein KTN1 and UPR.
Methods: All experiments were performed on keratinocytes models: HaCaT and HEK-A. ER lumen and the expression levels of KTN1 and UPR pathway proteins (PERK, IRE1α and ATF6) were examined by transmission electron microscopy and immunoblotting, respectively. 4-PBA, an UPR inhibitor, was used to detected its effects on DNA damage and cell proliferation. Subsequently, the effects of KTN1 deletion on UPR, DNA damage and cell proliferation after IR were detected. Tunicamycin was used to reactivate UPR and then we examined its effects on DNA damage.
Results: UPR was activated by IR in keratinocytes. Inhibition of UPR aggravated DNA damage and suppressed cell proliferation after IR. KTN1 expression was upregulated by IR and KTN1 depletion reduced ER expansion and the expression of UPR-related proteins. Moreover, KTN1 depletion aggravated DNA damage and suppressed cell proliferation after IR could reversed by reactivation of UPR.
Conclusion: KTN1 deletion aggravates IR-induced keratinocyte DNA damage via inhibiting UPR. Our findings provide new insights into the mechanisms of keratinocytes in response to IR-induced damage.
Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: DNA damage; Ionizing radiation; KTN1; Keratinocyte; Unfolded protein response
المشرفين على المادة: 0 (Membrane Proteins)
0 (KTN1 protein, human)
تواريخ الأحداث: Date Created: 20240306 Date Completed: 20240504 Latest Revision: 20240508
رمز التحديث: 20240509
DOI: 10.1016/j.jdermsci.2024.02.006
PMID: 38448340
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-569X
DOI:10.1016/j.jdermsci.2024.02.006