S-nitrosylated human alpha(1)-protease inhibitor

Area of Science:

• Biochemistry
• Immunology
• Physiology

Background:

• Alpha(1)-protease inhibitor (alpha(1)PI) is a key plasma protein involved in inhibiting proteases.
• Nitric oxide (NO) plays diverse physiological roles, including in inflammation and immune responses.
• The interaction between alpha(1)PI and NO under inflammatory conditions is not fully understood.

Purpose of the Study:

• To investigate the S-nitrosylation of alpha(1)PI by nitric oxide (NO).
• To characterize the biological activities of S-nitrosylated alpha(1)PI (S-NO-alpha(1)PI).
• To explore the potential role of S-NO-alpha(1)PI in innate defense mechanisms.

Main Methods:

• In vitro S-nitrosylation of human alpha(1)PI with NO.
• Assessment of S-NO-alpha(1)PI formation in activated murine macrophages and ex vivo rat liver models.
• Evaluation of S-NO-alpha(1)PI's effects on rabbit aortic ring relaxation, platelet aggregation, and bacterial growth inhibition.

Main Results:

• Alpha(1)PI readily undergoes S-nitrosylation by NO without losing its protease inhibitory capacity.
• S-NO-alpha(1)PI induced dose-dependent relaxation of rabbit aorta and inhibited platelet aggregation.
• S-NO-alpha(1)PI demonstrated potent bacteriostatic effects against various bacteria, exceeding those of NO and other S-nitrosylated compounds.

Conclusions:

• S-NO-alpha(1)PI is formed under inflammatory conditions as a nitric oxide (NO) sink.
• S-NO-alpha(1)PI functions as a soluble factor in innate defense, possessing antibacterial activity and promoting blood flow.
• S-nitrosylation diversifies the cytoprotective functions of alpha(1)PI in vivo.