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Sex Differences in Biological Processes and Nitrergic Signaling in Mouse Brain

Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
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Biomedicines 2020, 8(5), 124; https://doi.org/10.3390/biomedicines8050124
Received: 4 April 2020 / Revised: 6 May 2020 / Accepted: 13 May 2020 / Published: 15 May 2020
(This article belongs to the Section Model Systems in Research and Development)
Nitric oxide (NO) represents an important signaling molecule which modulates the functions of different organs, including the brain. S-nitrosylation (SNO), a post-translational modification that involves the binding of the NO group to a cysteine residue, is a key mechanism of nitrergic signaling. Most of the experimental studies are carried out on male animals. However, significant differences exist between males and females in the signaling mechanisms. To investigate the sex differences in the SNO-based regulation of biological functions and signaling pathways in the cortices of 6–8-weeks-old mice, we used the mass spectrometry technique, to identify S-nitrosylated proteins, followed by large-scale computational biology. This work revealed significant sex differences in the NO and SNO-related biological functions in the cortices of mice for the first-time. The study showed significant SNO-induced enrichment of the synaptic processes in female mice, but enhanced SNO-related cytoskeletal processes in the male mice. Proteins, which were S-nitrosylated in the cortices of mice of both groups, were more abundant in the female brain. Finally, we investigated the shared molecular processes that were found in both sexes. This study presents a mechanistic insight into the role of S-nitrosylation in both sexes and provides strong evidence of sex difference in many biological processes and signalling pathways, which will open future research directions on sex differences in neurological disorders. View Full-Text
Keywords: sex; proteomics; S-nitrosylation; nitric oxide; posttranslational modification; cell signaling; brain disorders; systems biology; computational biology sex; proteomics; S-nitrosylation; nitric oxide; posttranslational modification; cell signaling; brain disorders; systems biology; computational biology
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Khaliulin, I.; Kartawy, M.; Amal, H. Sex Differences in Biological Processes and Nitrergic Signaling in Mouse Brain. Biomedicines 2020, 8, 124.

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