Influence of human amylin on the membrane stability of rat primary hippocampal neurons

Zhang, Nan1,2; Xing, Yuan3,4; Yu, Yongzhou5; Liu, Chao6; Jin, Baohua5; Huo, Lifang5; Kong, Dezhi5; Yang, Zuxiao5; Zhang, Xiangjian7,8; Zheng, Ruimao9; Jia, Zhanfeng10; Kang, Lin11; Zhang, Wei5

2020-05-31

10.18632/aging.103105

Aging-US   影响因子和分区

1945-4589

The two most common aging-related diseases, Alzheimer's disease and type 2 diabetes mellitus, are associated with accumulation of amyloid proteins (beta-amyloid and amylin, respectively). This amylin aggregation is reportedly cytotoxic to neurons. We found that aggregation of human amylin (hAmylin) induced neuronal apoptosis without obvious microglial infiltration in vivo. High concentrations of hAmylin irreversibly aggregated on the surface of the neuronal plasma membrane. Long-term incubation with hAmylin induced morphological changes in neurons. Moreover, hAmylin permeabilized the neuronal membrane within 1 min in a manner similar to Triton X-100, allowing impermeable fluorescent antibodies to enter the neurons and stain intracellular antigens. hAmylin also permeabilized the cell membrane of astrocytes, though more slowly. Under scanning electron microscopy, we observed that hAmylin destroyed the integrity of the cell membranes of both neurons and astrocytes. Additionally, it increased intracellular reactive oxygen species generation and reduced the mitochondrial membrane potential. Thus, by aggregating on the surface of neurons, hAmylin impaired the cell membrane integrity, induced reactive oxygen species production, reduced the mitochondrial membrane potential, and ultimately induced neuronal apoptosis.

hAmylin hippocampal neurons mitochondrial membrane potential (mt Delta psi) Integrity of plasma membrane ROS

SCI

英语

通讯

National Science Foundation of China (NSFC)[81573416][81872848][81571080] ; National Major Special Project on New Drug Innovation of China[2018ZX09711001-004-003] ; National Science Foundation of Hebei Province[H2018206641][H2016206581][H2015206240] ; Project of the Education Bureau of Hebei Province[ZD2016088] ; Construction Program of Hebei Scientific Conditions[17963002D] ; science and technology research project of colleges and universities of Hebei Province[BJ2019026]

Cell Biology ; Geriatrics & Gerontology

Cell Biology ; Geriatrics & Gerontology

WOS:000537718700010

IMPACT JOURNALS LLC

Web of Science

1.Hebei Med Univ, Cent Lab, Hosp 1, Shijiazhuang, Hebei, Peoples R China
2.Hebei Int Joint Res Ctr Brain Sci, Shijiazhuang, Hebei, Peoples R China
3.Hebei Med Univ, Dept Neurol, Hosp 1, Shijiazhuang, Hebei, Peoples R China
4.Brain Aging & Cognit Neurosci Key Lab Hebei Prov, Shijiazhuang, Hebei, Peoples R China
5.Hebei Med Univ, Inst Chinese Integrat Med, Dept Pharmacol, Shijiazhuang, Hebei, Peoples R China
6.Hebei Med Univ, Dept Lab Anim Sci, Hebei Key Lab Lab Anim Sci, Shijiazhuang, Hebei, Peoples R China
7.Hebei Med Univ, Dept Neurol, Hebei Key Lab Vasc Homeostasis, Hosp 2, Shijiazhuang, Hebei, Peoples R China
8.Hebei Med Univ, Dept Neurol, Hebei Collaborat Innovat Ctr Cardiocerebrovasc Di, Hosp 2, Shijiazhuang, Hebei, Peoples R China
9.Peking Univ, Key Lab Neurosci Natl Hlth Commiss, Minist Educ,Key Lab Neurosci, Dept Anat Histol & Embryol,Hlth Sci Ctr,Neurosci, Beijing, Peoples R China
10.Hebei Med Univ, Key Lab Neural & Vasc Biol,Minist Educ, Inst Med Sci & Hlth,Ctr Innovat Drug Res & Evalua, Dept Pharmacol,Key Lab New Drug Pharmacol & Toxic, Shijiazhuang, Hebei, Peoples R China
11.Southern Univ Sci & Technol, Clin Med Res Ctr, Shenzhen Peoples Hosp,Jinan Univ, Dept Endocrinol,Clin Med Coll 2,Affiliated Hosp 1, Shenzhen, Peoples R China

Zhang, Nan,Xing, Yuan,Yu, Yongzhou,et al. Influence of human amylin on the membrane stability of rat primary hippocampal neurons[J]. Aging-US,2020,12(10):8923-8938.

Zhang, Nan.,Xing, Yuan.,Yu, Yongzhou.,Liu, Chao.,Jin, Baohua.,...&Zhang, Wei.(2020).Influence of human amylin on the membrane stability of rat primary hippocampal neurons.Aging-US,12(10),8923-8938.

Zhang, Nan,et al."Influence of human amylin on the membrane stability of rat primary hippocampal neurons".Aging-US 12.10(2020):8923-8938.