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亮氨酸通过激活PI3K/Akt通路介导自噬体-溶酶体融合并改善精子活力。

Leucine mediates autophagosome-lysosome fusion and improves sperm motility by activating the PI3K/Akt pathway.

作者信息

Zhang Jin, Zhang Xuemei, Liu Yingjie, Su Zihao, Dawar Farman Ullah, Dan Hong, He Yan, Gui Jian-Fang, Mei Jie

机构信息

College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Wuhan 430072, China.

出版信息

Oncotarget. 2017 Dec 4;8(67):111807-111818. doi: 10.18632/oncotarget.22910. eCollection 2017 Dec 19.

DOI:10.18632/oncotarget.22910
PMID:29340093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5762361/
Abstract

Amino acid supplementation is an efficient and effective strategy to increase sperm quality. In our research, a comparative study was conducted to screen free amino acids to improve sperm motility, and we found that leucine was the most efficient one. Leucine treatment increases sperm motility depending on the activation of PI3K/Akt signaling pathway, while the chemical inhibitor of PI3K/Akt signal could reduce the amount of pAkt activated by leucine treatment. Moreover, leucine treatment improved the expression of P62 and LC3-II, substantially suppressed the autophagy process in zebrafish testis. studies showed that leucine could reduce the fusion of autophagosome and lysosome that was indicated by the co-localization of EGFP-LC3 and lysosome marker. Two chemical modulators of autophagy, such as LY294002 (the inhibitor of PI3K/Akt signal) and chloroquine were administered to investigate the process of autophagy on zebrafish sperm motility. LY294002 inhibited autophagosome formation to reduced sperm motility, while chloroquine inhibited the fusion of autophagosome and lysosome to improve sperm motility. Our data suggest that short-term treatment with leucine could increase zebrafish sperm motility by affecting the autophagy and inhibiting the fusion of autophagosome and lysosomes, depending on the activation of PI3K/Akt signaling pathway.

摘要

补充氨基酸是提高精子质量的一种有效策略。在我们的研究中，进行了一项比较研究以筛选游离氨基酸来改善精子活力，我们发现亮氨酸是最有效的一种。亮氨酸处理通过激活PI3K/Akt信号通路来增加精子活力，而PI3K/Akt信号的化学抑制剂可减少亮氨酸处理激活的pAkt量。此外，亮氨酸处理改善了P62和LC3-II的表达，显著抑制了斑马鱼睾丸中的自噬过程。研究表明，亮氨酸可减少自噬体与溶酶体的融合，这通过EGFP-LC3与溶酶体标记物的共定位来表明。使用两种自噬化学调节剂，如LY294002（PI3K/Akt信号抑制剂）和氯喹，来研究自噬对斑马鱼精子活力的影响。LY294002抑制自噬体形成从而降低精子活力，而氯喹抑制自噬体与溶酶体的融合从而提高精子活力。我们的数据表明，短期用亮氨酸处理可通过影响自噬并抑制自噬体与溶酶体的融合来增加斑马鱼精子活力，这依赖于PI3K/Akt信号通路的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/a87d9f552194/oncotarget-08-111807-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/9962bcb4f2e1/oncotarget-08-111807-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/da7a12f23dc7/oncotarget-08-111807-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/ebe0a6aae503/oncotarget-08-111807-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/ab0c1c7493be/oncotarget-08-111807-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/e2f8e293874b/oncotarget-08-111807-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/c488b7383732/oncotarget-08-111807-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/3a00fe341282/oncotarget-08-111807-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/a87d9f552194/oncotarget-08-111807-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/9962bcb4f2e1/oncotarget-08-111807-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/da7a12f23dc7/oncotarget-08-111807-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/ebe0a6aae503/oncotarget-08-111807-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/ab0c1c7493be/oncotarget-08-111807-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/e2f8e293874b/oncotarget-08-111807-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/c488b7383732/oncotarget-08-111807-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/3a00fe341282/oncotarget-08-111807-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2989/5762361/a87d9f552194/oncotarget-08-111807-g008.jpg

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