• J K Pal

      Articles written in Journal of Biosciences

    • Association of HSP90 with the heme-regulated eukaryotic initiation factor 2α kinase—A collaboration for regulating protein synthesis

      J K Pal S Anand J Joseph

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      Among the various heat shock proteins (HSPs), members of the HSP70 and HSP90 families have drawn particular attention due to their heat shock-unrelated functions. HSP90, an ubiquitous and abundant member of the HSP90 family has been shown to be associated with a large array of protein factors. These proteins reside in the nucleus as well as in the cytoplasm and are involved in various physiological processes, such as, regulation of chromatin structure, cell cycle, cytoskelelal architecture, protein trafficking and protein synthesis. In this article, we focus our interest on the role of HSP90 in protein synthesis. Recent data obtained from a few laboratories strongly suggest that HSP90 interacts with the heme-regulated eukaryotic initiation factor 2α (elF-2α) kinase, also called the heme-regulated inhibitor, and causes its activation which leads to inhibition of protein synthesis. On the basis of data reported from various laboratories, including our own, we propose a possible model on the mechanism of HSP90-mediated activation of heme-regulated inhibitor and regulation of protein synthesis.

    • Heme-regulated eukaryotic initiation factor 2α kinase—A molecular indicator of haemolytic anemia

      S Anand J K Pal

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      The heme-regulated enkaryotic initiation factor-2α (eIF-2α) kinase, also called the heme-regulated inhibitor (HRI), is a key regulator of protein synthesis in mammalian reticulocyte. HRI is almost undetectable in blood samples of normal rabbits and it increases by 12–15-fold in the reticulocytes of anemic rabbits. In order to determine if such an increase in the quantity of HRI is gradual during anemia, and if it could be an indicator of anemia, we have carried out a detailed analysis on the expression of HRI and its eIF-2α kinase activity in rabbit reticulocyte lysates during various stages of acetylphenylhydrazine (APH)-induced anemia. In a 9-day schedule of induction of anemia, using an anti-HRI monoclonal antibody, HRI was detectable immediately after completion of fourth injection (day 5) and it increased gradually during the entire period reaching its maximum (24-fold) on day 9. Furthermore, when rabbits recovered from anemia due to individual response to the drug, quantity of HRI decreased significantly. Northern blot analysis results were similar to those of the Western blot. The other parameters that are generally used to monitor anemia in human patients, namely, reticulocyte count, haematocrit level and haemoglobin content although changed at the onset of anemia, did not change significantly during its progression. These results thus indicate that HRI could be a more appropriate and sensitive indicator of drug-induced anemia.

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