Key result
The traditional classification of nitric oxide synthase isoforms as strictly constitutive (NOS1, NOS3) or inducible (NOS2) may be overly restrictive, as evidence shows non-canonical expression patterns.
The traditional classification of NOS isoforms as strictly constitutive or inducible is overly simplistic, and recognizing non-canonical expression patterns may aid in developing targeted therapies for various disease states.
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Questions rigid NOS isoform classification in disease; leaves open whether non-canonical patterns warrant revised therapeutic targeting.
Science can move ahead by questioning established or canonical views and, so it may be with the enzymes, nitric oxide synthases (NOS). Nitric oxide (NO) is generated by NOS isoforms that are often described by their tissue-specific expression patterns. NOS1 (nNOS) is abundant in neural tissue, NOS2 is upregulated in activated macrophages and known as inducible NOS (iNOS), and NOS3 (eNOS) is abundant in endothelium where it regulates vascular tone. These isoforms are described as constitutive or inducible, but in this perspective we question the broad application of these labels. Are there instances where "constitutive" NOS (NOS1 and NOS3) are inducibly expressed; conversely, are there instances where NOS2 is constitutively expressed? NOS1 and NOS3 inducibility may be linked to post-translational regulation, making their actual patterns activity much more difficult to detect. Constitutive NOS2 expression has been observed in several tissues, especially the human pulmonary epithelium where it may regulate airway tone. These data suggest that expression of the three NOS enzymes may include non-established patterns. Such information should be useful in designing strategies to modulate these important enzymes in different disease states.
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Mattila et al. (2014) reported a review. Nitric oxide synthase (NOS) isoforms was evaluated. The traditional classification of nitric oxide synthase isoforms as strictly constitutive (NOS1, NOS3) or inducible (NOS2) may be overly restrictive, as evidence shows non-canonical expression patterns.
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