engleski

Metallothioneins and heat shock protein gp96 as sensors of stress and toxin-induced damages

The metallothionein (MT) family is a class of intracellular, cysteine-rich proteins presenting high affinity for metal ions, whose expression has been implicated as a transient response to any form of stress or injury providing cytoprotective action. Similarly, endoplasmic reticulum resident glycoprotein, gp96 participates as molecular chaperon in the control of protein synthesis and transport through the various cellular compartments. Moreover, as carriers of antigenic moieties such as peptides, gp96 has the ability to modulate the cellular immune response and activate the professional antigen-presenting cells, resulting in the production of pro-inflammatory cytokines and up-regulation of costimulatory molecules. In an attempt to elucidate some aspects of these events in this study, we investigated the effects of airborne pollutant-gasoline vapor on MT and gp96 expression in exposed tissue, as well as in the liver, brain, kidney and lymphatic tissues. Experiments were done on C57/BL6 mice, which were as a group of six animals for one h/day closed in a small metabolic chamber, containing soda lime for absorption of CO2 and ventilated with fresh air. Protocol was repeated for three or 10 days and then gp96, metallothioneins I+II (MT) and phenotype of lymphoid cells were detected in the liver, thymus and spleen by immunohistological staining and FACScan analysis. Simultaneously the cytotoxicity of intrahepatic and splenic mononuclear lymphatic cells was tested against syngeneic thymocytes and NK-sensitive targets (YAC-1). The findings were compared with data obtained in unstressed mice, living in the normal laboratory conditions. Inhalation of gasoline significantly upregulated the MT expression in the alveolar epithelia, kidney, as well as in the brain (hippocampus, astrocytes). However, stress provoked by restriction, also increased the MT and gp96 expression in the hepatocytes and gp96 expression in the spleen and thymus, where extensive surface staining was found on cells in the cortical and corticomedullar zones. Simultaneously, in the liver accumulated NKT and NK cells and hepatic MNLC became more cytotoxic against the syngeneic thymocytes (p<0.01), and less cytotoxic against the YAC-1 target. The data emphasize the protective role of MT and suggest that gp96-associated peptide in the liver, participate in activation of cytotoxicity against altered self. (Supported by grants from Croatian Ministry of Science, project No 0062018).

metallothioneins I+II; heat shock protein gp96; stress; inhalation; gasoline

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