Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in cerebrospinal fluid of AIDS patients with neuronal destruction.
BACKGROUND
14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed.


METHODS
In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting.


RESULTS
We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3).


CONCLUSIONS
These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.
Wakabayashi
H
H
Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, 770-8503, Tokushima, Japan.
Yano
M
M
Tachikawa
N
N
Oka
S
S
Maeda
M
M
Kido
H
H
D048948:14-3-3 Proteins; D000163:Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid* / Q000473:pathology*; D000328:Adult; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D003586:Cytomegalovirus Infections / Q000134:cerebrospinal fluid / Q000473:pathology; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000134:cerebrospinal fluid / Q000473:pathology; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D011237:Predictive Value of Tests; D020033:Protein Isoforms; D012697:Serine Endopeptidases / Q000134:cerebrospinal fluid*; D014446:Tyrosine 3-Monooxygenase / Q000134:cerebrospinal fluid*
D048948:14-3-3 Proteins; D020033:Protein Isoforms; D014446:Tyrosine 3-Monooxygenase; D012697:Serine Endopeptidases