Changes in cardiac mitochondrial aldehyde dehydrogenase 2 activity in relation to oxidative stress and inflammatory injury in diabetic rats

Wang,Hong-Ju; Kang,Pin-Fang; Wu,Wen-Juan; Tang,Yang; Pan,Qiang-Qiang; Ye,Hong-Wei; Tang,Bi; Li,Zheng-Hong; Gao,Qin

doi:10.3892/mmr.2013.1524

Changes in cardiac mitochondrial aldehyde dehydrogenase 2 activity in relation to oxidative stress and inflammatory injury in diabetic rats

Authors:
- Hong-Ju Wang
- Pin-Fang Kang
- Wen-Juan Wu
- Yang Tang
- Qiang-Qiang Pan
- Hong-Wei Ye
- Bi Tang
- Zheng-Hong Li
- Qin Gao
View Affiliations

Affiliations: Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, P.R. China, Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, P.R. China, Department of Physiology, Bengbu Medical College, Anhui 233030, P.R. China, Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Anhui 233030, P.R. China
Published online on: June 14, 2013 https://doi.org/10.3892/mmr.2013.1524
Pages: 686-690

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to determine the changes in mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity in relation to oxidative stress and inflammatory injury in different stages of diabetes mellitus (DM) in rats and to investigate the related mechanisms. DM in Sprague-Dawley (SD) rats was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin (STZ). The rats were randomly allocated into a control group, as well as into DM4w, DM8w and DM12w groups containing DM rats 4, 8 and 12 weeks after DM induction, respectively. Ventricular hemodynamic parameters were recorded; fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were determined using an automatic biochemistry analyzer; plasma interleukin (IL)-1, IL-4 and cardiac 4-hydroxynon-2-enal (4-HNE) levels were determined using enzyme-linked immunosorbent assay (ELISA), and cardiac ALDH2 activity was measured. The mRNA expression levels of Bax and Bcl-2 of the left anterior myocardium were detected by reverse transcriptase‑polymerase chain reaction (RT-PCR). FBG and HbA1c levels were increased in the DM groups compared to the control group. FBG levels were not significantly different among the DM4w, DM8w and DM12w groups, while HbA1c levels were increased with the progression of diabetes. The left ventricular developed pressure (LVDP), heart rate (HR) and rate-pressure product (RPP) were decreased, plasma IL-1 levels were increased, while IL-4 levels were decreased in the DM groups compared to the control group. Additionally, cardiac 4-HNE levels were increased, and ALDH2 activity was decreased in the DM groups compared to the control group. Bax mRNA levels were increased, Bcl-2 mRNA levels were decreased, and Bcl-2/Bax mRNA ratios were decreased in the DM groups compared to the control group. Moreover, LVDP, HR, RPP, IL-4, ALDH2 activity and Bcl-2/Bax mRNA ratios were further reduced, while 4-HNE and IL-1 levels were increased with the progression of diabetes. In conclusion, our results indicated that cardiac ALDH2 activity was further decreased with the progression of diabetes, which might be related to the increase of oxidative stress, inflammatory injury and the occurrence of apoptosis.

View Figures

View References

1	Adeghate E, Schattner P and Dunn E: An update on the etiology and epidemiology of diabetes mellitus. Ann N Y Acad Sci. 1084:1–29. 2006. View Article : Google Scholar : PubMed/NCBI
2	Gremizzi C, Vergani A, Paloschi V and Secchi A: Impact of pancreas transplantation on type 1 diabetes-related complications. Curr Opin Organ Transplant. 15:119–123. 2010. View Article : Google Scholar : PubMed/NCBI
3	Boudina S and Abel ED: Diabetic cardiomyopathy revisited. Circulation. 115:3213–3223. 2007. View Article : Google Scholar : PubMed/NCBI
4	Zgibor JC, Ruppert K, Orchard TJ, Soedamah-Muthu SS, Fuller J, Chaturvedi N and Roberts MS: Development of a coronary heart disease risk prediction model for type 1 diabetes: the Pittsburgh CHD in Type 1 diabetes risk model. Diabetes Res Clin Pract. 88:314–321. 2010. View Article : Google Scholar : PubMed/NCBI
5	Kaneto H, Katakami N, Matsuhisa M and Matsuoka TA: Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediators Inflamm. 2010:4538922010. View Article : Google Scholar : PubMed/NCBI
6	Penckofer S, Schwertz D and Florczak K: Oxidative stress and cardiovascular disease in type 2 diabetes: the role of antioxidants and pro-oxidants. J Cardiovasc Nurs. 16:68–85. 2002. View Article : Google Scholar : PubMed/NCBI
7	Ren J: Acetaldehyde and alcoholic cardiomyopathy: lessons from the ADH and ALDH2 transgenic models. Novartis Found Symp. 285:69–79. 2007. View Article : Google Scholar : PubMed/NCBI
8	Budas GR, Disatnik MH and Mochly-Rosen D: Aldehyde dehydrogenase 2 in cardiac protection: a new therapeutic target? Trends Cardiovasc Med. 19:158–164. 2009. View Article : Google Scholar : PubMed/NCBI
9	Forman HJ, Fukuto JM, Miller T, Zhang H, Rinna A and Levy S: The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys. 477:183–195. 2008. View Article : Google Scholar : PubMed/NCBI
10	Petersen DR and Doorn JA: Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radic Biol Med. 37:937–945. 2004. View Article : Google Scholar : PubMed/NCBI
11	Ma H, Li J, Gao F and Ren J: Aldehyde dehydrogenase 2 ameliorates acute cardiac toxicity of ethanol: role of protein phosphatase and forkhead transcription factor. J Am Coll Cardiol. 54:2187–2196. 2009. View Article : Google Scholar : PubMed/NCBI
12	Doser TA, Turdi S, Thomasm DP, Epstein PN, Li SY and Ren J: Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction. Circulation. 119:1941–1949. 2009. View Article : Google Scholar
13	Ge W, Guo R and Ren J: AMP-dependent kinase and autophagic flux are involved in aldehyde dehydrogenase-2-induced protection against cardiac toxicity of ethanol. Free Radic Biol Med. 51:1736–1748. 2011. View Article : Google Scholar : PubMed/NCBI
14	Churchill EN, Disatnik MH and Mochly-Rosen D: Time-dependent and ethanol-induced cardiac protection from ischemia mediated by mitochondrial translocation of varepsilonPKC and activation of aldehyde dehydrogenase 2. J Mol Cell Cardiol. 46:278–284. 2009. View Article : Google Scholar : PubMed/NCBI
15	Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD and Mochly-Rosen D: Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science. 321:1493–1495. 2008. View Article : Google Scholar : PubMed/NCBI
16	Budas GR, Disatnik MH, Chen CH and Mochly-Rosen D: Activation of aldehyde dehydrogenase 2 (ALDH2) confers cardioprotection in protein kinase C epsilon (PKCvarepsilon) knockout mice. J Mol Cell Cardiol. 48:757–764. 2010. View Article : Google Scholar : PubMed/NCBI
17	Wang J, Wang H, Hao P, Xue P, Wei S, Zhang Y and Chen Y: Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats. Mol Med. 17:172–179. 2011.PubMed/NCBI
18	Larsen CM, Faulenbach M, Vaag A, Ehses JA, Donath MY and Mandrup-Poulsen T: Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 32:1663–1668. 2009. View Article : Google Scholar : PubMed/NCBI
19	Zaitsev SV, Appelskog IB, Kapelioukh IL, Yang SN, Köhler M, Efendic S and Berggren PO: Imidazoline compounds protect against interleukin 1 beta-induced beta-cell apoptosis. Diabetes. 50:70–76. 2001. View Article : Google Scholar : PubMed/NCBI
20	Tas SW, Remans PH, Reedguist KA and Tak PP: Signal transduction pathways and transcription factors as therapeutic targets in inflammatory disease: towards innovative antirheumatic therapy. Curr Pharm Des. 11:581–611. 2005. View Article : Google Scholar : PubMed/NCBI
21	Lafaille JJ: The role of helper T cell subsets in autoimmune diseases. Cytokine Growth Factor Rev. 9:139–151. 1998. View Article : Google Scholar : PubMed/NCBI
22	Hart PH, Jones CA and Finlay-Jones JJ: Interleukin-4 suppression of monocyte tumour necrosis factor-alpha production. Dependence on protein synthesis but not on cyclic AMP production. Immunology. 76:560–565. 1992.PubMed/NCBI
23	Zhang M and Shah AM: Role of reactive oxygen species in myocardial remodeling. Curr Heart Fail Rep. 4:26–30. 2007. View Article : Google Scholar : PubMed/NCBI
24	Lee Y and Gustafsson AB: Role of apoptosis in cardiovascular disease. Apoptosis. 14:536–548. 2009. View Article : Google Scholar : PubMed/NCBI
25	Stewart MJ, Malek K and Crabb DW: Distribution of messenger RNAs for aldehyde dehydrogenase 1, aldehyde dehydrogenase 2, and aldehyde dehydrogenase 5 in human tissues. J Investig Med. 44:42–46. 1996.PubMed/NCBI
26	Esterbauer H, Schaur RJ and Zollner H: Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1:81–128. 1991. View Article : Google Scholar : PubMed/NCBI