Visiting Professor Manjit Dosanjh

Abstract:

Heat shock proteins (HSP) are a family of proteins whose synthesis is induced after environmental stresses such as heat, oxidizing agents, and exogenous factors, such as ethanol, smoke, drugs. Also inflammation is characterized by production of HSPs. Though their functions are not fully understood, they act as molecular chaperones facilitating the assembly of multi-protein complexes, and promoting the translocation of polypeptides across cell membranes. Since psoriasis is a frequently observed cutaneous inflammatory disorder, it has been considered a useful inflammatory model to investigate HSPs in this work. In particular HSP 70 and HSP 27 have been studied by Western blotting assay on fibroblast cultures. Biopsies were taken from psoriatic plaques before, during and after PUVA treatment; from non sun-exposed unaffected skin of four psoriatic patients before PUVA-therapy and from non sun-exposed skin of four controls. An increase of expression of HSPs in fibroblast cultures was demonstrated both in psoriatic skin and in particular after PUVA-treatment. The highest levels of HSPs coincided, after PUVA-therapy, in all the patients with the resolution of the lesions. Only slight levels of both HSP 70 and HSP 27 were found in fibroblast cultures derived from uninvolved skin before PUVA-therapy in psoriatic patients. The controls failed to present levels of HPS70, or had unremarkable levels of HSP27. Albeit preliminary, these results suggest that increased levels of HSPs, known to be pro-inflammatory molecules, may characterize the healing phase of an inflammatory disease such as psoriasis.

Abstract:

The effects of two substituted polychlorinated biphenyls, the 3,4,5,3',4,5' (PCB-169) and the 2,3,4,2',4',5' (PCB-138) forms, were examined on the expression of c-myc, c-jun, c-ras, and jun-b in 3T3-L1 cells. Northern blot analysis demonstrated that the two PCBs, which exhibit a coplanar and di-ortho-substituted configuration, activated these oncogenes differently. PCB-138 markedly induced overexpression of ras, jun, and myc, whereas PCB-169 led to the overexpression of jun-b. High-performance liquid chromatography analysis of the cell samples treated in medium without serum revealed a higher intracellular concentration of the 2,3,4,2',4',5'-hexachlorobiphenyl (hexaCB), whereas the 3,4,5,3',4'5'-hexaCB reached the same concentration in the sonicated samples of cells with or without serum. These results indicated that there was a relationship between PCB structure, bioavailability, and the capacity to stimulate oncogene expression.