지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 632 - 644 (13page)
이용수
초록· 키워드
오류제보하기
The molecular mechanism underlying autophagy impairment in the retinal pigment epithelium (RPE) in dry age-related macular degeneration (AMD) is not yet clear. Based on the causative role of poly(ADP-ribose) polymerase 1 (PARP1) in RPE necrosis, this study examined whether PARP1 is involved in the autophagy impairment observed during dry AMD pathogenesis. We found that autophagy was downregulated following H2O2-induced PARP1 activation in ARPE-19 cells and olaparib, PARP1 inhibitor, preserved the autophagy process upon H2O2 exposure in ARPE-19 cells. These findings imply that PARP1 participates in the autophagy impairment upon oxidative stress in ARPE-19 cells. Furthermore, PARP1 inhibited autolysosome formation but did not affect autophagosome formation in H2O2-exposed ARPE-19 cells, demonstrating that PARP1 is responsible for impairment of late-stage autophagy in particular. Because PARP1 consumes NAD+ while exerting its catalytic activity, we investigated whether PARP1 impedes autophagy mediated by sirtuin1 (SIRT1), which uses NAD+ as its cofactor. A NAD+ precursor restored autophagy and protected mitochondria in ARPE-19 cells by preserving SIRT1 activity upon H2O2. Moreover, olaparib failed to restore autophagy in SIRT1-depleted ARPE-19 cells, indicating that PARP1 inhibits autophagy through SIRT1 inhibition. Next, we further examined whether PARP1-induced autophagy impairment occurs in the retinas of dry AMD model mice. Histological analyses revealed that olaparib treatment protected mouse retinas against sodium iodate (SI) insult, but not in retinas cotreated with SI and wortmannin, an autophagy inhibitor. Collectively, our data demonstrate that PARP1-dependent inhibition of SIRT1 activity impedes autophagic survival of RPE cells, leading to retinal degeneration during dry AMD pathogenesis.
목차
등록된 정보가 없습니다.
참고문헌 (53)
참고문헌 신청
Abd Elmageed, Z. Y. / 2012 / The poly(ADP-ribose)polymerases(PARPs) : new roles in intracellular transport / Cell. Signal 24:1~8
Bai, P. / 2011 / PARP-1inhibition increases mitochondrial metabolism through SIRT1 activation / Cell Metab 13:461~468
Borra, M. T. / 2005 / Mechanism of human SIRT1activation by resveratrol / J. Biol. Chem 280:17187~17195
Cao, D. / 2015 / Structural basis for allosteric, substrate-dependent stimulation of SIRT1activity by resveratrol / Genes Dev 29:1316~1325
Cerutti, R. / 2014 / NAD(+)-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease / Cell Metab 19:1042~1049
Bai, P. / 2011 / PARP-1inhibition increases mitochondrial metabolism through SIRT1 activation / Cell Metab 13:461~468
Borra, M. T. / 2005 / Mechanism of human SIRT1activation by resveratrol / J. Biol. Chem 280:17187~17195
Cao, D. / 2015 / Structural basis for allosteric, substrate-dependent stimulation of SIRT1activity by resveratrol / Genes Dev 29:1316~1325
Cerutti, R. / 2014 / NAD(+)-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease / Cell Metab 19:1042~1049
함께 읽어보면 좋을 논문
논문 유사도에 따라 DBpia 가 추천하는 논문입니다. 함께 보면 좋을 연관 논문을 확인해보세요!
-
Overview of the Minireviews on Autophagy
Molecules and Cells
2018 .01
-
The autophagy research in electron microscopy
한국현미경학회지
2019 .01
-
Autophagy and Oral Cancer
생명과학회지
2017 .08
-
The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes
Molecules and Cells
2018 .01
-
Autophagy and Longevity
Molecules and Cells
2018 .01
-
Lipopolysaccharide (LPS)-Induced Autophagy Is Responsible for Enhanced Osteoclastogenesis
Molecules and Cells
2017 .11
-
Autophagy Dysregulation and Obesity-Associated Pathologies
Molecules and Cells
2018 .01
-
Autophagy Is Pro-Senescence When Seen in Close-Up, but Anti-Senescence in Long-Shot
Molecules and Cells
2017 .09
-
Emerging Paradigm of Crosstalk between Autophagy and the Ubiquitin-Proteasome System
Molecules and Cells
2017 .12
-
Effects of in vitro vitamin D treatment on function of T cells and autophagy mechanisms in high-fat diet-induced obese mice
Nutrition Research and Practice
2021 .12
-
Effects of in vitro vitamin D treatment on function of T cells and autophagy mechanisms in high-fat diet-induced obese mice
Nutrition Research and Practice
2021 .12
-
PKA regulates autophagy through lipolysis during fasting
Molecules and Cells
2024 .01
-
A Novel Reciprocal Crosstalk between RNF168 and PARP1 to Regulate DNA Repair Processes
Molecules and Cells
2018 .08
-
Crosstalk and Interplay between the Ubiquitin-Proteasome System and Autophagy
Molecules and Cells
2017 .07
-
우울증에서 자가소화작용의 역할
생명과학회지
2022 .10
-
Autophagy in Mycobacterium abscessus Infection
JOURNAL OF BACTERIOLOGY AND VIROLOGY
2017 .09
-
Induction of cytoprotective autophagy by morusin via AMP-activated protein kinase activation in human non-small cell lung cancer cells
Nutrition Research and Practice
2020 .10
-
Induction of cytoprotective autophagy by morusin via AMP-activated protein kinase activation in human non-small cell lung cancer cells
Nutrition Research and Practice
2020 .10
-
Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line
Genes & Genomics
2021 .10
-
Ginsenoside Rg1 Induces Autophagy in Colorectal Cancer through Inhibition of the Akt/mTOR/p70S6K Pathway
Journal of Microbiology and Biotechnology
2024 .04
이 논문의 저자 정보
최근 본 자료
댓글(0)
0