Abstract
AIDS has several manifestations in the gastrointestinal tract — 2′,3′-dideoxycytidine (ddC) as an anti-AIDS drug will a/lso produce some effects on the alimentary tract: it causes inflammation. The analysis of the expression of the heat shock proteins (hsp60 and hsp70) is a new marker of the inflammation caused by external stress. The hsp60 is located mainly in the mitochondria; hsp70 is found in both cytoplasm and the mitochondria. The aim of the present study was to reveal whether ddC can produce any expressive biochemical changes in the oral cavity or generally in the gastrointestinal tract.
Methods
The rats were treated with intraperitoneal administration of 1 mg ddC/day for two weeks. The animals were killed by cervical dislocation, then the buccal, lingual, oesophageal, gastric, duodenal and colon mucosae were removed, and frozen in liquid nitrogen. Protein extract was obtained and separated by SDS—PAGE, followed by the Western blotting of the proteins to the nitrocellulose membrane. After binding the first antibody (mouse-derived anti-heat shock protein), a second antibody was administered (anti-mouse IgG, labelled with peroxidase). The antigen—antibody reaction was detected by 3,3’diaminobenzidine tetrahydrochloride dihydrate.
Results
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1.
In the control and in the treated groups, the hsp60 monoclonal antibody binding was visible in the oesophageal, gastric, duodenal and colon mucosae, but, in the buccal and lingual mucosae, it was not detectable in the treated group.
-
2.
The hsp70 was detectable in every tissue of both treated and non-treated groups. To verify whether the cause was indirect oxidative damage, the NADH-dihydrogenase (complex I), cytochromeoxidoreductase (complex III) and cytochrome-oxidase (complex IV), members of the respiratory chain, were examined but no alterations were found. Our results indicate that the disappearance of hsp60 in the oral cavity is a unique phenomenon following ddC treatment. This damage might be caused by the ddC interaction with hsp60; however, the exact mechanism is not yet known.
Correspondence
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References
De Vivo DC. The expanding clinical spectrum of mitochondrial diseases. Brain Devel. 1993; 15: 1.
Zeviani M, Gellera C, Antozzi C et al. Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA. Lancet. 1991; 338: 143–7.
Helbert M, Fletcher T, Peddle B, Harris JR, Pinching AJ. Zidovudine-associated myopathy. Lancet. 1988; 2 (8612): 689–90.
Herskowitz A, Willoughby SB, Baughman KL, Schulman SP, Bartlett JD. Cardiomyopathy associated with antiretroviral therapy in patients with HIV infection: A report of six cases. Ann Intern Med. 1992; 116: 311–13.
Hirsch MS, D’Aquila RT. Therapy for human immunodeficiency virus infection. N Engl J Med. 1993; 328: 1686–95.
Carper SW, Duffy JJ, Gerner EW. Heat shock proteins in thermotolerance and other cellular processes. Cancer Res. 1987; 47: 5249–55.
Bhattacharyya T, Karnezis A, Murphy SP et al. Cloning and subcellular localisation of human mitochondrial hsp70. J Biol Chem. 1995; 270: 1705–10.
Knowlton AA. Heat shock proteins, stress, and the heart. Ann NY Acad Sci. 1994; 723: 128–37.
Pelham H. Activation of heat-shock genes in eukaryotes. Trends Genet. 1985; 1: 31–5.
Jacquier-Sarlin MR, Fuller K, Dinh-Xuan AT, Richard M-J, Polla BS. Protective effect of hsp70 in inflammation. Experientia. 1994; 50: 1031–8.
Hall TJ. Role of hsp70 in cytokine production. Experientia. 1994; 50: 1048–53.
Feige U, Polla BS. Heat shock proteins: the hsp70 family. Experientia. 1994; 50: 979–86.
Wynn RM, Davie JR, Cox RP, Chuang DT. Molecular chaperons: Heat shock proteins, foldases and matchmakers. J Lab Clin Med. 1994; 124: 31–6.
Burel C, Mezger V, Pinto M, Rallu M, Trigon S, Morange N. Mammalian heat shock protein families. Expression and function. Experientia. 1992; 48: 629–33.
Becker J, Craig EA. Heat shock proteins as molecular chaperones. Eur J Biochem. 1994; 219: 11–23.
Craig EA, Gambill BD, Nelson RJ. Heat shock proteins: Molecular chaperons of protein biogenesis. Microbiol Rev. 1993; 57: 402–14.
Stuart RA, Cyr DM, Neupert W. Hsp70 in mitochondrial biogenesis: From chaperoning nascent polypeptide chains to facilitation of protein degradation. Experientia. 1994; 50: 1002–11.
Santoro GM. Heat shock proteins and virus replication: hsp70s as mediators of the antiviral effects of prostaglandins. Experientia. 1994; 50: 1039–47.
Sumegi B, Butwell NB, Malloy CR, Sherry AD. Lipoamide influences substrate selection in postischaemic perfused rat hearts. Biochem J. 1992; 297: 109–13.
Boog CJP, de Graeff-Mееdeг ER, Voorhorst-Ogink M, van Kooten PJS, Geuze HJ, van Eden W. Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis. J Exp Med. 1992; 175: 1805–10.
Velez-Granell CS, Arias AE, Torres-Ruiz JA, Bendayan M. Molecular chaperons in pancreatic tissue: the presence of cpn10, cpn60 and hsp70 in distinct compartments along the secretory pathway of the acinar cells. J Cell Sci. 1994; 107; 539–49.
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© 1997 Springer Science+Business Media Dordrecht
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Csere, P., Varbiro, G., Sumegi, B., Mózsik, G. (1997). Aids Treatment and the Heat Shock Protein Level in the Gastrointestinal Tract. In: Gaginella, T.S., Mózsik, G., Rainsford, K.D. (eds) Biochemical Pharmacology as an Approach to Gastrointestinal Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5390-4_23
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DOI: https://doi.org/10.1007/978-94-011-5390-4_23
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