Perivascular iron deposits are associated with protein nitration in cerebral experimental autoimmune...

Area of Science:

• Neuroscience
• Immunology
• Biochemistry

Background:

• Protein nitration is linked to tissue damage in multiple sclerosis (MS).
• While peroxynitrite is a suspected mediator, iron, heme, or heme-associated molecules can also catalyze protein nitration independently.
• MS patients exhibit central nervous system (CNS) microhemorrhages and perivascular iron deposits.

Purpose of the Study:

• To investigate the association between iron and protein nitration in the CNS.
• To explore the role of iron-catalyzed nitration in the pathogenesis of MS.

Main Methods:

• Utilized a cerebral experimental autoimmune encephalomyelitis (cEAE) mouse model, which mimics MS-related perivascular iron deposits.
• Employed histochemical staining for iron and immunohistochemistry for nitrotyrosine, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) on cerebral sections.
• Assessed blood-brain barrier (BBB) integrity by examining albumin extravasation using immunohistochemistry.

Main Results:

• Iron deposits were found to co-localize with nitrotyrosine staining around blood vessels in cEAE mice.
• Control animals showed minimal iron and nitrotyrosine staining.
• Albumin extravasation, indicative of BBB leakage, was observed in cEAE mice but not in controls.
• Iron deposits were also associated with eNOS and iNOS, suggesting potential sources for nitration reactions.

Conclusions:

• Iron-catalyzed protein nitration is a likely mechanism contributing to CNS tissue damage in MS.
• Perivascular iron deposits in MS may directly promote protein nitration.
• Albumin leakage across the BBB in MS may offer incomplete protection by binding iron/heme or serving as a nitration target.