Skip to main content

Advertisement

SpringerLink
Log in

Reduced expression of GSTM2 and increased oxidative stress in spontaneously hypertensive rat

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The spontaneously hypertensive rat (SHR) is a well-characterized experimental model for essential hypertension. By comparative proteomics, we previously identified glutathione S-transferase, mu 2 (GSTM2), a protein involved in detoxification of reactive oxygen species, which had a significant reduction in left ventricles of 16-week-old SHR compared with WKY rats. In parallel, Western blotting and RT-PCR showed a similar reduction of GSTM2 in left ventricles and aortas of 4-, 8-, and 16-week-old SHR, which is before the onset of hypertension. This suggests that differential expression is not attributable to long-term changes in blood pressure. Meanwhile, the activities of GSTM2 were significantly decreased in different ages old SHR. Conversely, there was an enhanced generation of superoxide anion and activation of NADPH oxidase in SHR, which was accompanied by an increase in the protein expression of p47phox, a subunit of NADPH oxidase. These data suggest that it maybe a reduction in antioxidant defenses, evident by a reduced expression and activity of GSTM2, in the left ventricles and aortas of SHR that leads to increased levels of superoxide anion and activation of NADPH oxidase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Pereira LM, Mandarim-de-Lacerda CA (2001) Stereology of cardiac hypertrophy induced by NO blockade in rats treated with enalapril and verapamil. Anal Quant Cytol Histol 23:330–338

    PubMed  CAS  Google Scholar 

  2. Ito N, Nitta Y, Ohtani H et al (1994) Remodelling of microvessels by coronary hypertension or cardiac hypertrophy in rats. J Mol Cell Cardiol 26:49–59

    Article  PubMed  CAS  Google Scholar 

  3. Okamoto K, Aoki K (1963) Development of a strain of spontaneously hypertensive rats. Jpn Circ J 27:282–293

    PubMed  CAS  Google Scholar 

  4. Hu WY, Han YJ, Gu LZ et al (2007) Involvement of Ras-regulated myosin light chain phosphorylation in the captopril effects in spontaneously hypertensive rats. Am J Hypertens 20:53–61

    Article  PubMed  CAS  Google Scholar 

  5. Rothermund L, Paul M (1998) Hypertension and the rennin angiotensin system evidence from genetic and transgenic studies. Basic Res Cardiol 93:1–6

    Article  PubMed  CAS  Google Scholar 

  6. Rysa J, Leskinen H, Ilves M et al (2005) Distinct upregulation of extracellular matrix genes in transition from hypertrophy to hypertensive heart failure. Hypertension 45:927–933

    Article  PubMed  Google Scholar 

  7. Mitchell GF, Pfeffer JM, Pfeffer MA (1997) The transition to failure in the spontaneously hypertensive rat. Am J Hypertens 10:120S–126S

    PubMed  CAS  Google Scholar 

  8. Zhou SG, Zhou SF, Huang HQ et al (2006) Proteomic analysis of hypertrophied myocardial protein patterns in renovascularly hypertensive and spontaneously hypertensive rats. J Proteome Res 5:2901–2908

    Article  PubMed  CAS  Google Scholar 

  9. McBride MW, Carr FJ, Graham D et al (2003) Microarray analysis of rat chromosome 2 congenic strains. Hypertension 41:847–853

    Article  PubMed  CAS  Google Scholar 

  10. Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:445–600

    Article  PubMed  CAS  Google Scholar 

  11. Hurst R, Bao Y, Jemth P et al (1998) Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferases. Biochem J 332:97–100

    PubMed  CAS  Google Scholar 

  12. Sharma R, Yang Y, Sharma A et al (2004) Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal 6:289–300

    Article  PubMed  CAS  Google Scholar 

  13. Lacy F, O’Connor DT, Schmid-Schonbein GW (1998) Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens 16:291–303

    Article  PubMed  CAS  Google Scholar 

  14. Russo C, Olivieri O, Girelli D et al (1998) Anti-oxidant status and lipid peroxidation in patients with essential hypertension. J Hypertens 16:1267–1271

    Article  PubMed  CAS  Google Scholar 

  15. Redon J, Oliva MR, Tormos C et al (2003) Antioxidant activities and oxidative stress byproducts in human hypertension. Hypertension 41:1096–1101

    Article  PubMed  CAS  Google Scholar 

  16. Chan SH, Tai MH, Li CY et al (2006) Reduction in molecular synthesis or enzyme activity of superoxide dismutases and catalase contributes to oxidative stress and neurogenic hypertension in spontaneously hypertensive rats. Free Radic Biol Med 40:2028–2039

    Article  PubMed  CAS  Google Scholar 

  17. Kerr S, Brosnan MJ, McIntyre M et al (1999) Superoxide anion production is increased in a model of genetic hypertension: role of the endothelium. Hypertension 33:1353–1358

    PubMed  CAS  Google Scholar 

  18. Swei A, Lacy F, Delano FA et al (1999) A mechanism of oxygen free radical production in the Dahl hypertensive rat. Microcirculation 6:179–187

    Article  PubMed  CAS  Google Scholar 

  19. Bishop JE, Kiernan LA, Montgomery HE et al (2000) Raised blood pressure, not rennin–angiotensin systems, causes cardiac fibrosis in TGR m(Ren2)27 rats. Cardiovasc Res 47:57–67

    Article  PubMed  CAS  Google Scholar 

  20. Del Monte F, Butler K, Boecker W et al (2002) Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure. Physiol Genomics 9:49–56

    PubMed  Google Scholar 

  21. Kuo WH, Chou FP, Young SC et al (2005) Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes. Toxicol Appl Pharmacol 208:155–162

    Article  PubMed  CAS  Google Scholar 

  22. Habig WH, Pabst MJ, Jakoby WB (1974) The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    PubMed  CAS  Google Scholar 

  23. Cifuentes ME, Rey FE, Carretero OA et al (2000) Upregulation of p67phox and gp91phox in aortas from angiotensin II-infused mice. Am J Physiol Heart Circ Physiol 279:H2234–H2240

    PubMed  CAS  Google Scholar 

  24. Jalil JE, Perez A, Ocaranza MP et al (2005) Increased aortic NADPH oxidase activity in rats with genetically high angiotensin converting enzyme levels. Hypertension 46:1362–1367

    Article  PubMed  CAS  Google Scholar 

  25. Tarpey MM, Wink DA, Grisham MB (2004) Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. Am J Physiol Regul Integr Comp Physiol 286:R431–R444

    PubMed  CAS  Google Scholar 

  26. Virdis A, Neves MF, Amiri F et al (2004) Role of NAD(P)H oxidase on vascular alterations in angiotensin II-infused mice. J Hypertens 22:535–542

    Article  PubMed  CAS  Google Scholar 

  27. Van Heerebeek L, Meischl C, Stooker W et al (2002) NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system? J Clin Pathol 55:561–568

    Article  PubMed  Google Scholar 

  28. Lassegue B, Clempus RE (2003) Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 285:R277–R297

    PubMed  CAS  Google Scholar 

  29. Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189

    Article  PubMed  CAS  Google Scholar 

  30. Touyz RM, Yao G, Schiffrin EL (2003) c-Src induces phosphorylation and translocation of p47phox: role in superoxide generation by angiotensin II in human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 23:981–987

    Article  PubMed  CAS  Google Scholar 

  31. Zhao T, Singhal SS, Piper JT et al (1999) The role of human glutathione S-transferases hGSTA1-1 and hGSTA2-2 in protection against oxidative stress. Arch Biochem Biophys 367:216–224

    Article  PubMed  CAS  Google Scholar 

  32. Hayes JD, McLellan LI (1999) Glutathione and glutathione-dependent enzymes represent a coordinately regulated defence against oxidative stress. Free Radic Res 31:273–300

    Article  PubMed  CAS  Google Scholar 

  33. Hamilton CA, Brosnan MJ, McIntyre M et al (2001) Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension 37:529–534

    PubMed  CAS  Google Scholar 

  34. Sawyer DB, Siwik DA, Xiao L et al (2002) Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol 34:379–388

    Article  PubMed  CAS  Google Scholar 

  35. Moreau P, Tea BS, Dam TV et al (1997) Altered balance between cell replication and apoptosis in hearts and kidneys of newborn SHR. Hypertension 30:720–724

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Fund of PR of China (No.: 30472022), Major program in key field of people’s government of GuangDong province, PR of China (No.: 2003A30904), Doctor’s scientific research start fund of GuangDong Pharmaceutical University, PR of China (No.: 43540140), and Medical scientific research fund of GuangDong province, PR of China (No.: A2007309).

Author information

Authors and Affiliations

  1. Pharmacology and Toxicology Laboratory, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan II Road, GuangZhou, 510080, P.R. China

    Si-Gui Zhou, Ping Wang, Rong-Biao Pi, Jie Gao, Jia-Jia Fu, Jian Fang, Jia Qin, Hui-Jie Zhang, Rui-Fang Li, Shao-Rui Chen, Fu-Tian Tang & Pei-Qing Liu

  2. Department of Pharmacology, GuangDong Pharmaceutical University, GuangZhou, 510006, China

    Si-Gui Zhou

Authors
  1. Si-Gui Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rong-Biao Pi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia-Jia Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jia Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hui-Jie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rui-Fang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shao-Rui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Fu-Tian Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pei-Qing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pei-Qing Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, SG., Wang, P., Pi, RB. et al. Reduced expression of GSTM2 and increased oxidative stress in spontaneously hypertensive rat. Mol Cell Biochem 309, 99–107 (2008). https://doi.org/10.1007/s11010-007-9647-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9647-7

Keywords

Search

Navigation