Heat Shock Proteins as Modulators of Pancreatitis

Heat shock proteins (HSPs) are highly conserved proteins, which are expressed in response to stress in all the species. Ritossa in 1962 (31), was first to observe an altered puffing pattern in giant chromosomes of salivary glands in Drosophila busckii after heat shock. On microscopic evaluation, areas of increased transcriptional activity in these giant chromosomes appear swollen and are called puffs. He reported that temperature shock induced well defined variation in the normal puffing patterns, which is observed during the development of Drosophila larvae. After initiation of heat shock, incorporation of Hcytidine in puffs started within 3-4 minutes and reached maximum after 10 minutes. In addition to heat shock, this effect could also be reproduced by treatment with 2,4-dinitrophenol (DNP) and sodium salicylate. After the initial report, this important work remained largely ignored till it was rediscovered in 1974. Tissieres et al (38), while studying synthesis of proteins by metabolic incorporation of radioactive precursors, observed a new pattern of radiolabeled protein synthesis following heat shock. These new proteins were termed as “heat shock” proteins. It was observed that heat shock activated synthesis of only a few polypeptides and strongly inhibited the synthesis of most others. Subsequently, it was found that this family of proteins is up-regulated in response to variety of stresses like heat stress, inflammation, ischemia, anoxia and heavy metals and now these are commonly called heat stress proteins (HSPs). HSPs are subdivided according to their molecular size (from 10kDa till 100 kDa e.g. HSP110, HSP90 (HSP90a, HSP90b. GRP94), HSP70 (HSP70, HSC70, mHSP70 (GRP75), GRP78) (21, 22, 43), HSP60 (6), HSP40 (7, 30), HSP27 (35) and HSP10 (GroES) (13, 15) and contains both constitutively expressed members as well as polypeptides whose expression increases many folds in response to stress.