title: Changes in cardiac mitochondrial aldehyde dehydrogenase 2 activity in relation to oxidative stress and inflammatory injury in diabetic rats.
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.
authors.affiliation: Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, P.R. China.
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Wang
authors.forename: Pin-Fang
authors.initials: PF
authors.lastname: Kang
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Tang
authors.forename: Qiang-Qiang
authors.initials: QQ
authors.lastname: Pan
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Ye
authors.forename: Bi
authors.initials: B
authors.lastname: Tang
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000097:blood; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005786:Gene Expression Regulation; D006442:Glycated Hemoglobin / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007375:Interleukin-1; D015847:Interleukin-4; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C505112:Aldh2 protein, rat; C027576:4-hydroxy-2-nonenal