A novel polymorphism in nitric oxide synthase interacting protein (NOSIP) modulates nitric oxide and mortality in Human Sepsis

Mukherjee, Ratnadeep; Singh, Diwakar Kumar; Patra, Rajkumar; Barman, Pijus Kanti; Prusty, Birendra Kumar; Thatoi, Pravat; Tripathy, Rina; Das, Bidyut Kumar; Ravindran, Balachandran

Nitric oxide, synthesised by three isoforms of Nitric Oxide synthases viz., nNOS by neurons, eNOS by endothelial cells and iNOS by phagocytes, performs a wide variety of biological functions in neurons, vascular endothelial cells and immune cells. Interaction between inducible nitric oxide synthase (iNOS) and Nitric oxide synthase interacting protein (NOSIP) was observed both in human monocytes and mouse macrophages and in cell free systems by biophysical methods. A novel mutation in nitric oxide synthase interacting protein (NOSIP) determined NO levels produced by human monocytes and was associated with disease severity in Sepsis patients. The study reveals NOSIP as an important regulator of inflammation by virtue of its ability to influence nitric oxide production both in mice and in humans and opens up novel avenues for therapeutic strategies against acute inflammation. While the influence of this novel NOSIP polymorphism in cardio-vascular and neuronal functions could be a subject of future investigations, its role in determining disease severity and mortality of the ongoing Covid 19 pandemic will be of immediate relevance.