Microtubule proteins and their post-translational forms in the cerebrospinal fluid of patients with paraparesis associated with HTLV-I infection and in SH-SY5Y cells: an in vitro model of HTLV-I-induced disease.
HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by axonal degeneration of the corticospinal tracts. The specific requirements for transport of proteins and organelles to the distal part of the long axon are crucial in the corticospinal tracts. Microtubule dysfunction could be involved in this disease, configuring an axonal transport disease. We measured tubulin and its post-translational modified forms (acetylated and tyrosinated) in CSF of patients and controls, as well as tau and its phosphorylated forms. There were no significant differences in the contents of tubulin and acetyl-tubulin between patients and controls; tyrosyl-tubulin was not detected. In HAM/TSP, tau levels were significantly reduced, while the ratio of pT181/total tau was higher in patients than in controls, this being completely different from what is reported in other neurodegenerative diseases. Phosphorylation at T181 was also confirmed by Mass Spectrometry analysis. Western Blotting with monospecific polyclonal antibodies against pS199, pT205, pT231, pS262, pS356, pS396, pS404 and pS422 did not show differences in phosphorylation in these residues between patients and controls. Treating human SH-SY5Y neuroblastoma cells, a well-known in vitro neurite retraction model, with culture supernatant of MT-2 cells (HTLV-I infected cell line that secretes the viral Tax protein) we observed neurite retraction and an increase in tau phosphorylation at T181. A disruption of normal phosphorylation of tau protein in T181 could result in its dysfunction, contributing to axonal damage.
Maldonado
Horacio
H
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Química y Farmacéuticas, Universidad de Chile, Santiago, Chile.
Ortiz-Riaño
Emilio
E
Krause
Bernardo
B
Barriga
Andrés
A
Medina
Fernando
F
Pando
M Elsa
ME
Alberti
Carolina
C
Kettlun
Ana M
AM
Collados
Lucía
L
García
Lorena
L
Cartier
Luis
L
Valenzuela
M Antonieta
MA
D000368:Aged; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D015368:Human T-lymphotropic virus 1; D006801:Humans; D015151:Immunoblotting; D013058:Mass Spectrometry; D008875:Middle Aged; D016501:Neurites / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000134:cerebrospinal fluid*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D013997:Time Factors; D014404:Tubulin / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D014404:Tubulin; D016875:tau Proteins