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CYP2E1-mediated oxidative stress regulates HO-1 and GST expression in maneb- and paraquat-treated rat polymorphonuclear leukocytes.
Mol Cell Biochem. 2014 Aug; 393(1-2):209-22.MC

Abstract

Cytochrome P4502E1 (CYP2E1), glutathione-S-transferase A4-4 (GSTA4-4), and inducible nitric oxide synthase (iNOS) are implicated in maneb- and paraquat-induced toxicity leading to various pathological conditions. The study aimed to investigate the role of CYP2E1 in maneb- and paraquat-induced oxidative stress in rat polymorphonuclear leukocytes (PMNs) and its crosstalk with iNOS-mediated nitrosative stress and GSTA4-4-linked protective effect, if any and their consequent links with the nuclear factor erythoid 2-related factor 2 (Nrf2) activation and heme oxygenase-1 (HO-1) expression. Rats were treated with/without maneb and/or paraquat for 1, 2, and 3 weeks along with vehicle controls. Subsets of rats were also treated with diallyl sulfide (DAS) or aminoguanidine (AG) along with the respective controls. Maneb and paraquat augmented the reactive oxygen species (ROS), lipid peroxidation (LPO) and 4-hydroxy nonenal (4-HNE) contents, and superoxide dismutase (SOD) activity in the PMNs. However, maneb and paraquat attenuated the reduced glutathione (GSH) level and the expression/activity of total GST and GST-pi. Maneb and paraquat increased the expression/activity of CYP2E1, GSTA4-4, iNOS, Nrf2 and HO-1, and nitrite content. CYP2E1 inhibitor, DAS noticeably alleviated maneb- and paraquat-induced ROS, LPO, 4-HNE, SOD, Nrf2 and HO-1, GST, GSH, and GST-pi while iNOS, nitrite content and GSTA4-4 levels were unchanged. Conversely, AG, an iNOS inhibitor, attenuated maneb- and paraquat-directed changes in nitrite, LPO, iNOS but it did not alter ROS, GSH, SOD, GST, GST-pi, Nrf2, HO-1, CYP2E1, and GSTA4-4. The results demonstrate that CYP2E1 induces iNOS-independent free radical generation and subsequently modulates the Nrf2-dependent HO-1 and 4-HNE-mediated GST expression in maneb- and paraquat-treated PMNs.

Authors+Show Affiliations

Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Post Box- 80, Lucknow, Uttar Pradesh, 226 001, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24771067

Citation

Ahmad, Israr, et al. "CYP2E1-mediated Oxidative Stress Regulates HO-1 and GST Expression in Maneb- and Paraquat-treated Rat Polymorphonuclear Leukocytes." Molecular and Cellular Biochemistry, vol. 393, no. 1-2, 2014, pp. 209-22.
Ahmad I, Shukla S, Singh D, et al. CYP2E1-mediated oxidative stress regulates HO-1 and GST expression in maneb- and paraquat-treated rat polymorphonuclear leukocytes. Mol Cell Biochem. 2014;393(1-2):209-22.
Ahmad, I., Shukla, S., Singh, D., Chauhan, A. K., Kumar, V., Singh, B. K., Patel, D. K., Pandey, H. P., & Singh, C. (2014). CYP2E1-mediated oxidative stress regulates HO-1 and GST expression in maneb- and paraquat-treated rat polymorphonuclear leukocytes. Molecular and Cellular Biochemistry, 393(1-2), 209-22. https://doi.org/10.1007/s11010-014-2062-y
Ahmad I, et al. CYP2E1-mediated Oxidative Stress Regulates HO-1 and GST Expression in Maneb- and Paraquat-treated Rat Polymorphonuclear Leukocytes. Mol Cell Biochem. 2014;393(1-2):209-22. PubMed PMID: 24771067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CYP2E1-mediated oxidative stress regulates HO-1 and GST expression in maneb- and paraquat-treated rat polymorphonuclear leukocytes. AU - Ahmad,Israr, AU - Shukla,Smriti, AU - Singh,Deepali, AU - Chauhan,Amit Kumar, AU - Kumar,Vinod, AU - Singh,Brajesh Kumar, AU - Patel,Devendra Kumar, AU - Pandey,Haushila Prasad, AU - Singh,Chetna, Y1 - 2014/04/27/ PY - 2013/12/24/received PY - 2014/04/11/accepted PY - 2014/4/29/entrez PY - 2014/4/29/pubmed PY - 2015/2/13/medline SP - 209 EP - 22 JF - Molecular and cellular biochemistry JO - Mol Cell Biochem VL - 393 IS - 1-2 N2 - Cytochrome P4502E1 (CYP2E1), glutathione-S-transferase A4-4 (GSTA4-4), and inducible nitric oxide synthase (iNOS) are implicated in maneb- and paraquat-induced toxicity leading to various pathological conditions. The study aimed to investigate the role of CYP2E1 in maneb- and paraquat-induced oxidative stress in rat polymorphonuclear leukocytes (PMNs) and its crosstalk with iNOS-mediated nitrosative stress and GSTA4-4-linked protective effect, if any and their consequent links with the nuclear factor erythoid 2-related factor 2 (Nrf2) activation and heme oxygenase-1 (HO-1) expression. Rats were treated with/without maneb and/or paraquat for 1, 2, and 3 weeks along with vehicle controls. Subsets of rats were also treated with diallyl sulfide (DAS) or aminoguanidine (AG) along with the respective controls. Maneb and paraquat augmented the reactive oxygen species (ROS), lipid peroxidation (LPO) and 4-hydroxy nonenal (4-HNE) contents, and superoxide dismutase (SOD) activity in the PMNs. However, maneb and paraquat attenuated the reduced glutathione (GSH) level and the expression/activity of total GST and GST-pi. Maneb and paraquat increased the expression/activity of CYP2E1, GSTA4-4, iNOS, Nrf2 and HO-1, and nitrite content. CYP2E1 inhibitor, DAS noticeably alleviated maneb- and paraquat-induced ROS, LPO, 4-HNE, SOD, Nrf2 and HO-1, GST, GSH, and GST-pi while iNOS, nitrite content and GSTA4-4 levels were unchanged. Conversely, AG, an iNOS inhibitor, attenuated maneb- and paraquat-directed changes in nitrite, LPO, iNOS but it did not alter ROS, GSH, SOD, GST, GST-pi, Nrf2, HO-1, CYP2E1, and GSTA4-4. The results demonstrate that CYP2E1 induces iNOS-independent free radical generation and subsequently modulates the Nrf2-dependent HO-1 and 4-HNE-mediated GST expression in maneb- and paraquat-treated PMNs. SN - 1573-4919 UR - https://www.unboundmedicine.com/medline/citation/24771067/CYP2E1_mediated_oxidative_stress_regulates_HO_1_and_GST_expression_in_maneb__and_paraquat_treated_rat_polymorphonuclear_leukocytes_ L2 - https://doi.org/10.1007/s11010-014-2062-y DB - PRIME DP - Unbound Medicine ER -