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Biotechnology and Applied Biochemistry (2002) 36, (57–62) (Printed in Great Britain)

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The haem-regulated eukaryotic initiation factor 2a kinase: a molecular indicator of lead-toxicity anaemia in rabbits

Sanjay Anand¹ and Jayanta K. Pal²

Department of Biotechnology, University of Pune, Pune-411 007, India

Key words: eIF-2a kinase activity, expression, haem-regulated inhibitor, heat-shock protein, regulation of protein synthesis.

Abbreviations used: eIF-2a, eukaryotic initiation factor 2a; Hsp, heat-shock protein; HRI, haem-regulated inhibitor; APH, acetylphenylhydrazine; PCV, packed cell volume.

¹Present address: Department of Dairy and Animal Science, The Pennsylvania State University, University Park, PA 16802, U.S.A.

²To whom correspondence should be addressed (e-mail jkpal@unipune.ernet.in).

The haem-regulated eukaryotic initiation factor 2a kinase, also called the haem-regulated inhibitor (HRI), has been shown to increase in the peripheral blood cells as a function of drug-induced anaemia in rabbits, suggesting that it could be a molecular indicator of drug-induced anaemia [Anand and Pal (1997) J. Biosci. 22, 287–298]. In the present investigation, we have determined the expression of HRI during lead-induced anaemia in rabbits. The level of anaemia has been determined by routine procedures such as reticulocyte count, haemoglobin content and packed cell volume. These values were compared with the results obtained for a quantitative Western blot of HRI in the blood cell lysates of drug- and lead-induced anaemic rabbits. These results indicate that HRI could be used as a molecular marker for lead-induced anaemia since a progressive increase in HRI levels could be detected as a function of the time of lead exposure. In order to understand the role of stress proteins, heat-shock protein (Hsp) 70 and Hsp90, in inducing anaemia during lead exposure, levels of Hsp70 and Hsp90, and their interaction with HRI, have been determined. Increased levels of these proteins and their intermolecular complexes with HRI suggest their role in regulating protein synthesis during lead-induced anaemia. These observations further reiterate the use of HRI as a potential indicator for drug- and heavy-metal-induced anaemia in humans.

Received 6 February 2002/7 May 2002; accepted 9 May 2002

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