Amyloid fibril formation by macrophage migration inhibitory factor

Journal Article · Fri Dec 16 04:00:00 EST 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2005.1· OSTI ID:20793223

Lashuel, Hilal A ^[1]; Aljabari, Bayan ^[2]; Sigurdsson, Einar M ^[3]; Metz, Christine N ^[2]; Lin, Leng ^[4]; Callaway, David J.E. ^[2]; Bucala, Richard ^[4]

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1. Integrative Biosciences Institute, Laboratory of Molecular Neurobiology and Neuroproteomics, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne (Switzerland)
2. North Shore Long Island Jewish Research Institute, 300 Community Drive, Manhasset, NY (United States)
3. New York University, School of Medicine, Departments of Psychiatry and Pathology, 560 First Avenue, New York, NY (United States)
4. Yale University School of Medicine, 300 Cedar Street, New Haven, CT (United States)

We demonstrate herein that human macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine expressed in the brain and not previously considered to be amyloidogenic, forms amyloid fibrils similar to those derived from the disease associated amyloidogenic proteins {beta}-amyloid and {alpha}-synuclein. Acid denaturing conditions were found to readily induce MIF to undergo amyloid fibril formation. MIF aggregates to form amyloid-like structures with a morphology that is highly dependent on pH. The mechanism of MIF amyloid formation was probed by electron microscopy, turbidity, Thioflavin T binding, circular dichroism spectroscopy, and analytical ultracentrifugation. The fibrillar structures formed by MIF bind Congo red and exhibit the characteristic green birefringence under polarized light. These results are consistent with the notion that amyloid fibril formation is not an exclusive property of a select group of amyloidogenic proteins, and contribute to a better understanding of the factors which govern protein conformational changes and amyloid fibril formation in vivo.

• OSTI ID: 20793223
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 338; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINES
AZO DYES
BIREFRINGENCE
BRAIN
CONFORMATIONAL CHANGES
ELECTRON MICROSCOPY
IN VIVO
INFLAMMATION
MACROPHAGES
PH VALUE
PROTEINS
SULFONIC ACIDS
ULTRACENTRIFUGATION