The Role of RAD6B and PEDF in Retinal Degeneration

被引：3

作者：

Ye, Qiang ^{[1
,2
]}

Wang, Jiaqi ^{[1
]}

Liu, Xiangwen ^{[1
]}

Liu, Zihua ^{[1
]}

BaZong, LuoSong ^{[2
]}

Ma, Jinhai ^{[2
]}

Shen, Rong ^{[1
]}

Ye, Weichun ^{[3
,4
]}

Zhang, Wenfang ^{[2
]}

Wang, Degui ^{[1
]}

机构：

[1] Lanzhou Univ, Basic Med Coll, Inst Human Anat & Histoembryol, 199 Donggang West Rd, Lanzhou 730000, Peoples R China

[2] Lanzhou Univ, Dept Ophthalmol, Hosp 2, 82 Cuiying Door, Lanzhou 730000, Peoples R China

[3] Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China

[4] Lanzhou Univ, Dept Chem, Lanzhou 730000, Peoples R China

来源：

NEUROSCIENCE | 2022年 / 480卷

基金：

中国国家自然科学基金;

关键词：

RAD6B; PEDF; retina; degeneration; senescence; apoptosis; EPITHELIUM-DERIVED FACTOR; INTRAOCULAR GENE-TRANSFER; DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; PIGMENT EPITHELIUM; TUMOR SUPPRESSION; HISTONE H2AX; CELL-DEATH; PHOTORECEPTORS; APOPTOSIS;

D O I：

10.1016/j.neuroscience.2021.11.010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

is an E2 ubiquitin-conjugating enzyme, playing an important role in DNA damage repair, gene expression, senescence, apoptosis and protein degradation. However, the specific mechanism between ubiquitin and retinal degeneration requires more investigation. Pigment epithelium-derived factor (PEDF) has a potent neurotrophic effect on the retina, protecting retinal neurons and photoreceptors from cell death caused by pathological damage. In this study, we found that loss of RAD6B leads to retinal degeneration in mice, especially in old age. Affymetrix microarray analysis showed that the PEDF signal was changed in RAD6B deficient groups. The expression of c-H2AX, b-Gal, P53, Caspase-3, P21 and P16 was increased significantly in retinas of RAD6B knockout (KO) mice. Our studies suggest that RAD6B and PEDF play an important role in the health of retina, whereas the absence of RAD6B accelerates the degeneration. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：19 / 31

页数：13

共 59 条

[31] RNF168 forms a functional complex with RAD6 during the DNA damage response [J].

Liu, Chao ;

Wang, Degui ;

Wu, Jiaxue ;

Keller, Jennifer ;

Ma, Teng ;

Yu, Xiaochun .

JOURNAL OF CELL SCIENCE, 2013, 126 (09) :2042-2051

[32] Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators [J].

Liu, Yangfan P. ;

Tsai, I. -Chun ;

Morleo, Manuela ;

Oh, Edwin C. ;

Leitch, Carmen C. ;

Massa, Filomena ;

Lee, Byung-Hoon ;

Parker, David S. ;

Finley, Daniel ;

Zaghlou, Norann A. ;

Franco, Brunella ;

Katsanis, Nicholas .

JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (05) :2059-2070

[33] Increased proteasomal activity supports photoreceptor survival in inherited retinal degeneration [J].

Lobanova, Ekaterina S. ;

Finkelstein, Stella ;

Li, Jing ;

Travis, Amanda M. ;

Hao, Ying ;

Klingeborn, Mikael ;

Skiba, Nikolai P. ;

Deshaies, Raymond J. ;

Arshavsky, Vadim Y. .

NATURE COMMUNICATIONS, 2018, 9

[34] Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration [J].

Lobanova, Ekaterina S. ;

Finkelstein, Stella ;

Skiba, Nikolai P. ;

Arshavsky, Vadim Y. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (24) :9986-9991

[35] Loss of RAD6B induces degeneration of the cochlea in mice [J].

Ma, Yangping ;

Song, Yanfeng ;

Shen, Rong ;

Li, Panpan ;

Ding, Han ;

Guo, Zhao ;

Liu, Xiangwen ;

Wang, Degui .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2020, 531 (03) :402-408

[36] γH2AX: a sensitive molecular marker of DNA damage and repair [J].

Mah, L-J ;

El-Osta, A. ;

Karagiannis, T. C. .

LEUKEMIA, 2010, 24 (04) :679-686

[37] Mice deficient in the Vici syndrome gene Epg5 exhibit features of retinitis pigmentosa [J].

Miao, Guangyan ;

Zhao, Yan G. ;

Zhao, Hongyu ;

Ji, Cuicui ;

Sun, Huayu ;

Chen, Yingyu ;

Zhang, Hong .

AUTOPHAGY, 2016, 12 (12) :2263-2270

[38] Inhibition of Nuclear Translocation of Apoptosis-Inducing Factor Is an Essential Mechanism of the Neuroprotective Activity of Pigment Epithelium-Derived Factor in a Rat Model of Retinal Degeneration [J].

Murakami, Yusuke ;

Ikeda, Yasuhiro ;

Yonemitsu, Yoshikazu ;

Onimaru, Mitsuho ;

Nakagawa, Kazunori ;

Kohno, Ri-ichiro ;

Miyazaki, Masanori ;

Hisatomi, Toshio ;

Nakamura, Makoto ;

Yabe, Takeshi ;

Hasegawa, Mamoru ;

Ishibashi, Tatsuro ;

Sueishi, Katsuo .

AMERICAN JOURNAL OF PATHOLOGY, 2008, 173 (05) :1326-1338

[39] RNF8 deficiency results in neurodegeneration in mice [J].

Ouyang, Siwei ;

Song, Yanfeng ;

Tian, Yingxia ;

Chen, Yibin ;

Yu, Xiaochun ;

Wang, Degui .

NEUROBIOLOGY OF AGING, 2015, 36 (10) :2850-2860

[40] A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage [J].

Paull, TT ;

Rogakou, EP ;

Yamazaki, V ;

Kirchgessner, CU ;

Gellert, M ;

Bonner, WM .

CURRENT BIOLOGY, 2000, 10 (15) :886-895

← 1 2 3 4 5 6 →