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Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme.
Arch Biochem Biophys. 1996 May 01; 329(1):39-46.AB

Abstract

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces acute renal proximal tubular necrosis, a consequence of free radical-mediated oxidative tissue damage, that eventually leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we investigated the free radical-induced oxidative stress response in this carcinogenesis model, focusing on the expression of glutathione S-transferases (GSTs) which catalyze the conjugation of reactive chemicals with glutathione and play an important role in protecting cells. A single intraperitoneal Fe-NTA treatment (15 mg Fe/kg body weight) induced a rapid oxidative stress, which was monitored by the accumulation of lipid peroxidation products and the loss of sulfhydryl contents in the kidneys, resulting in a 30% reduction of GST activity 1 h after an Fe-NTA treatment. The enzyme activity returned to the control level after 16 h. The immunoblot analysis of GST isozymes demonstrated that the level of alpha-class GSTs (GST-Ya and GST-Yc) and pi-class GST (GST-Yp), major GST isozymes constitutively produced in the kidney, decreased immediately within 1 h of the Fe-NTA treatment. The onset of the recovery of GST-Yp protein levels was detected 3 h after the Fe-NTA treatment. The enhanced production of GST-Yp in gene expression was evident in the drastic elevation of mRNA levels and these increases coincided with a substantial rise in the GST activity and protein levels. The alpha-class GSTs were not inducible by treatment with Fe-NTA. The immunohistochemical analysis demonstrated that the expression of GST-Yp was strongly induced in the regenerating proximal tubular cells. A steady accumulation of GST-Yp protein was observed in the subacute toxicity experiments with multiple injections of Fe-NTA. These results suggest that the enhanced expression of GST-Yp is important in mediating cell repairs or increasing the resistance to subsequent injury.

Authors+Show Affiliations

Laboratory of Food and Biodynamics, Nagoya University School of Agriculture, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8619633

Citation

Fukuda, A, et al. "Oxidative Stress Response in Iron-induced Renal Carcinogenesis: Acute Nephrotoxicity Mediates the Enhanced Expression of Glutathione S-transferase Yp Isozyme." Archives of Biochemistry and Biophysics, vol. 329, no. 1, 1996, pp. 39-46.
Fukuda A, Osawa T, Oda H, et al. Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme. Arch Biochem Biophys. 1996;329(1):39-46.
Fukuda, A., Osawa, T., Oda, H., Toyokuni, S., Satoh, K., & Uchida, K. (1996). Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme. Archives of Biochemistry and Biophysics, 329(1), 39-46.
Fukuda A, et al. Oxidative Stress Response in Iron-induced Renal Carcinogenesis: Acute Nephrotoxicity Mediates the Enhanced Expression of Glutathione S-transferase Yp Isozyme. Arch Biochem Biophys. 1996 May 1;329(1):39-46. PubMed PMID: 8619633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme. AU - Fukuda,A, AU - Osawa,T, AU - Oda,H, AU - Toyokuni,S, AU - Satoh,K, AU - Uchida,K, PY - 1996/5/1/pubmed PY - 1996/5/1/medline PY - 1996/5/1/entrez SP - 39 EP - 46 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 329 IS - 1 N2 - An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces acute renal proximal tubular necrosis, a consequence of free radical-mediated oxidative tissue damage, that eventually leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we investigated the free radical-induced oxidative stress response in this carcinogenesis model, focusing on the expression of glutathione S-transferases (GSTs) which catalyze the conjugation of reactive chemicals with glutathione and play an important role in protecting cells. A single intraperitoneal Fe-NTA treatment (15 mg Fe/kg body weight) induced a rapid oxidative stress, which was monitored by the accumulation of lipid peroxidation products and the loss of sulfhydryl contents in the kidneys, resulting in a 30% reduction of GST activity 1 h after an Fe-NTA treatment. The enzyme activity returned to the control level after 16 h. The immunoblot analysis of GST isozymes demonstrated that the level of alpha-class GSTs (GST-Ya and GST-Yc) and pi-class GST (GST-Yp), major GST isozymes constitutively produced in the kidney, decreased immediately within 1 h of the Fe-NTA treatment. The onset of the recovery of GST-Yp protein levels was detected 3 h after the Fe-NTA treatment. The enhanced production of GST-Yp in gene expression was evident in the drastic elevation of mRNA levels and these increases coincided with a substantial rise in the GST activity and protein levels. The alpha-class GSTs were not inducible by treatment with Fe-NTA. The immunohistochemical analysis demonstrated that the expression of GST-Yp was strongly induced in the regenerating proximal tubular cells. A steady accumulation of GST-Yp protein was observed in the subacute toxicity experiments with multiple injections of Fe-NTA. These results suggest that the enhanced expression of GST-Yp is important in mediating cell repairs or increasing the resistance to subsequent injury. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/8619633/Oxidative_stress_response_in_iron_induced_renal_carcinogenesis:_acute_nephrotoxicity_mediates_the_enhanced_expression_of_glutathione_S_transferase_Yp_isozyme_ DB - PRIME DP - Unbound Medicine ER -