Calpastatin is upregulated in non-immune neuronal cells via toll-like receptor 2 (TLR2) pathways by lipid-containing agonists.
Biochim Biophys Acta
; 1833(10): 2369-77, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23773963
Calpain (intracellular Ca(2+)-dependent protease) and calpastatin (calpain specific endogenous inhibitor) are widely distributed in biological systems, and have been implicated in many cellular physiological and pathological processes. Calpastatin level is of central importance to the control of calpain activity. We demonstrated for the first time that calpastatin is overexpressed in mycoplasma-contaminated cultured cells (SH-SY5Y cells that are infected by a strain of Mycoplasma hyorhinis (NDMh)). We have found that the calpastatin-upregulating activity resides in the mycoplasmal membrane lipoproteins, and is associated with NF-κB activation. Calpain-promoted proteolysis is attenuated in the NDMh lipoprotein-treated cells. Here we show that the NDMh lipoproteins promoted an increase in calpastatin in SH-SY5Y cells via the TLR2/TAK1/NF-κB pathway. The synthetic mycoplasmal lipopeptide MALP-2 and the bacterial lipopeptide PAM3CSK4 (TLR2 agonists) also promoted calpastatin upregulation. LPS (TLR4 agonist) activated NF-κB without calpastatin increase in the cell. In contrast, lipoteichoic acid (TLR2 agonist) upregulated calpastatin not via NF-κB activation, but via the MEK1/ELK1 pathway. Zymosan and peptidoglycan, TLR2 agonists that lack lipids, did not induce calpastatin upregulation. Cell treatment with a calpastatin-upregulating agonist (lipoteichoic acid) led to the attenuation of Ca(2+)-promoted calpain activity, whereas agonists that do not upregulate calpastatin (LPS, Zymosan) were ineffective. Overall, the results indicate that in these non-immune cells, calpastatin is upregulated by TLR2-agonists containing lipids, with more than one downstream pathway involved. Such agonists may be useful for studying mechanisms and factors involved in calpastatin regulation. In addition, suitable TLR2 agonists may be of interest in devising treatments for pathological processes involving excessive calpain activation.
Palavras-chave
Calpain; Calpastatin; LPP; LPS; LTA; Lipid TLR2 agonists; MALP-2; Mycoplasmal lipoproteins; NDMh; PAM3CSK4; PGN; TDE; TLR agonists; TLRs; lipopolysaccharide; lipoproteins; lipoteichoic acid; macrophage activating lipopeptide 2; neuroblastoma derived Mycoplasma hyorhinis; peptidoglycan; synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4; synthetic cell penetrating peptide TAT-DEF-ELK1; toll-like receptors
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
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Mycoplasma hyorhinis
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Receptor 2 Toll-Like
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Lipopeptídeos
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Neuroblastoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article