The 14-3-3 Protein Detectable in the Cerebrospinal Fluid of Patients with Prion-Unrelated Neurological Diseases Is Expressed Constitutively in Neurons and Glial Cells in Culture

Abstract

The 14-3-3 protein belongs to a family of 30-kD proteins originally identified by two-dimensional analysis of brain protein extracts. Recently, the detection of the 14-3-3 protein in the cerebrospinal fluid (CSF) is utilized as a highly reliable test for the premortem diagnosis of prion diseases such as Creutzfeldt-Jakob disease. For the initial step, to clarify the biological implication of the CSF 14-3-3 protein in these diseases, its expression was investigated in neural tissues and cultures and CSF samples from patients with a variety of neurological diseases by Western blot analysis and immunocytochemistry. The constitutive expression of the 14-3-3 protein was identified in all neural and nonneural tissues examined. It was expressed in all neurons, astrocytes, oligodendrocytes, and microglia in culture with its location in both cytoplasmic and nuclear regions. The 14-3-3 protein was detected in the CSF of 8 out of 71 patients, including 1 Gerstmann-Sträussler-Scheinker disease patient and 7 patients with prion-unrelated neurological diseases, such as meningoencephalitis of viral, bacterial, or tuberculous origin, multiple sclerosis, and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. These results suggest that the 14-3-3 protein expressed constitutively at substantial levels in both neurons and glial cells might be released into the CSF as a disease-nonspecific consequence of the extensive brain damage and indicate that the analysis of the 14-3-3 protein in the CSF is not useful as a screening test for prion diseases.

14-3-3σ associates with cell surface aminopeptidase N in the regulation of matrix metalloproteinase-1

“…Stratifin (SFN, or 14-3-3) is a member of a large family of highly conserved 14-3-3 proteins, which are known to function as intracellular chaperones in signal transduction, apoptosis and cell cycle regulation (Hermeking, 2003;Pozuelo et al, 2004). Several groups have reported on the presence of 14-3-3 proteins in the extracellular space (Butler and Overall, 2009a;Katz and Taichman, 1999;Kobayashi et al, 2009;Leffers et al, 1993;Satoh et al, 1999). Our group has recently identified a novel function for the keratinocyte-releasable form of SFN as a potent MMP-1-stimulatory factor in dermal fibroblasts (Ghahary et al, 2004).…”

Cerebrospinal fluid biomarkers in Guillain-Barré syndrome – Where do we stand?

“…Several neurological diseases including CJD are characterized by increased brain expression, deposition or CSF release of protein 14-3-3. Reports on CSF 14-3-3 in GBS are controversial, presumably due to methodological differences between the studies [2,62]. While CSF 14-3-3 could function as another unspecific marker of neuronal damage, clinical relevance in GBS seems to be small at the present state.…”

Fibroblast extracellular matrix gene expression in response to keratinocyte‐releasable stratifin

“…Although more than 100 proteins have been reported to interact with intracellular members of 14-3-3 family [Pozuelo et al, 2004], functional activities of the releasable forms of these proteins in general and 14-3-3 s, in particular, are completely unknown. In fact, the presence of 14-3-3 proteins in cerebral spinal fluid [Satoh et al, 1999] as well as KCM [Katz and Taichman, 1999] has been previously reported, without designating any function. Our group has recently identified and characterized a keratinocyte-releasable anti-fibrogenic factor (KDAF) for dermal fibroblasts, which was discovered to be a releasable form of stratifin.…”