NOS1 and Associated Diseases
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Overview of NOS1
Nitric oxide synthase 1 (NOS1, also known as neuronal NOS) is a protein coded by the NOS1 gene located at chromosome 12q24.2 in humans. NOS1 is a member of the nitric oxide synthases family with the capacity of synthesizing nitric oxide from L-arginine. NOS1 is widely expressed in the brain, peripheral nervous system, skeletal muscle, and so on. According to its enzymatic source and tissue location, nitric oxide, a reactive free radical, operates as a biological mediator in a number of processes with a variety of functions, including neurotransmission, as well as in antibacterial and anticancer effects. NOS1 has been associated with alternatively spliced transcript variants that encode several isoforms, some of which are exclusive to the testis.
NOS1 in Disease
Ectopic expression of NOS1 is associated with neural diseases such as Alzheimer’s disease and non-neural diseases such as ovarian cancer.
- Alzheimer’s disease
The miRNA-188/NOS1 axis plays important role in Alzheimer’s disease (AD). AD, as an irreversible neurodegenerative disease, is a public health issue in the world. Downregulated miRNA-188 is identified in mouse primary hippocampal neurons. The amyloid-beta-treated BV2 cell line can serve as the AD model for research. In this cell line, downregulated miRNA-188 and upregulated NOS1 can be observed and NOS1 is a target of miRNA-188. Overexpression of miRNA-188 can promote cell proliferation and inhibit apoptotic, whereas NOS1 can reverse the induction caused by miRNA-188. Berberine, which acts as the neuroprotective reagent, can alleviate the neuronal damage in the amyloid-beta-treated BV2 cell line via miR-188/NOS1 pathway. Taken together, the miR-188/NOS1 axis is associated with AD progression.
- Ovarian cancer
NOS1/ABCG2 axis is associated with the chemoresistance of ovarian cancer (OC). Multidrug resistance has been linked to ABCG2 at the molecular level in a variety of cancer forms, including ovarian cancer. Upregulated ABCG2 expression is induced in OC cells with the treatment of DDP. Numerous cancer processes including chemoresistance have been demonstrated to be accelerated by NOS1. In the gene expression profiles of chemo-resistant ovarian cancer, both NOS1 and ABCG2 are upregulated compared to the chemo-sensitive one. Overexpression of NOS1 induces the high expression of ABCG2, which is inhibited by the NOS1 selective inhibitor. Besides, NOS1 appears to enhance cell survival during the DDP treatment, which can be reversed by the addition of an ABCG2 inhibitor. In summary, NOS1/ABCG2 can partly mediate the chemoresistance of OC.
Fig.1 Both NOS1 and ABCG2 are enriched in chemo-resistant OC. (Li, 2018)
The NOS1 is crucial for a variety of biological functions. For the benefit of our clients, Creative Biolabs has our own expert teams working in the gene therapy industry. We offer thorough gene therapy development solutions for many diseases. Please feel free to contact us for more details about your NOS1 project.
References
- Chen, M.; et al. Berberine attenuates Aβ-induced neuronal damage through regulating miR-188/NOS1 in Alzheimer’s disease. Mol Cell Biochem. 2022, 474: 285–294.
- Li, X.; et al. NOS1 upregulates ABCG2 expression contributing to DDP chemoresistance in ovarian cancer cells. Oncol Lett. 2018.
