2. Academic Validation
  3. Microcystin-leucine-arginine induced neurotoxicity by initiating mitochondrial fission in hippocampal neurons

Microcystin-leucine-arginine induced neurotoxicity by initiating mitochondrial fission in hippocampal neurons

  • Sci Total Environ. 2020 Feb 10;703:134702. doi: 10.1016/j.scitotenv.2019.134702.
Changliang Zhang 1,  Jing Wang 1,  Jinling Zhu 1,  Yabing Chen 2,  Xiaodong Han 3
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China.
  • 2 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China. Electronic address: ybchen916218@126.com.
  • 3 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China. Electronic address: hanxd@nju.edu.cn.
PMID: 31753492 DOI: 10.1016/j.scitotenv.2019.134702
Abstract

Microcystin-leucine-arginine (MC-LR) can cross the blood-brain barrier (BBB) and demonstrate potent acute hippocampal neurotoxicity. Chronic exposure to MC-LR has been confirmed to cause learning and memory deficits in mice, but the potential molecular mechanism of MC-LR-caused neurotoxicity is still unclear. In this research, we observed that MC-LR induced oxidative stress, mitochondrial fission and Apoptosis in HT-22 hippocampal neurons. Moreover, further studies identified that MC-LR induced mitochondrial fragmentation via activating Dynamin-related protein 1 (Drp1) and Mitochondrial fission factor (Mff), contributing to Apoptosis of hippocampal neuronal cells. The observed effects were associated with increased intracellular CA2+ and reduced activity of protein phosphatases 2A (PP2A) as results of MC-LR exposure in hippocampal neuron cells. CA2+ activates CaMK II and Akt to enhance phosphorylation of Drp1 at Ser616 residue. Inhibition of PP2A activity increased AMPK activity to mediate phosphorylation of Mff. Our data proved that MC-LR can cause mitochondrial fragmentation in hippocampal neurons, which provides novel perception to explore the underlying molecular mechanism associated with MC-LR-induced neurotoxicity and Alzheimer's disease-like changes.

Keywords

Microcystin-LR; Mitochondrial dynamics; Neurotoxicity; Oxidative stress.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z