Author(s): Zhao ZQ, Nakamura M, Wang NP, Wilcox JN, Shearer S, et al.
Objective: The purpose of the present study was to investigate whether apoptosis is triggered during ischemia (I) and reperfusion (R) and whether I/R-induced apoptosis is correlated with changes in expression of Bcl-2 and Bax.
Methods: Anesthetized open-chest dogs were divided into two groups. Group I: 7 h of permanent I without R (PI, n = 7); Group II: 60 min I followed by 6 h R (I/R, n = 8). Apoptosis was identified as "DNA ladder" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end labeling (TUNEL) assay.
Results: Collateral myocardial coronary blood flow during I, confirmed by colored microspheres was comparable in both groups. Although PI caused 72 +/- 5% infarct size, very few TUNEL-positive cells were detected in the necrotic area (0.2 +/- 0.1% of total normal nuclei), consistent with an absence of DNA laddering. In contrast, the appearance of TUNEL-positive cells was significantly displayed after 6 h R in the necrotic area in I/R group (26 +/- 4%, P < 0.001 vs. PI group), and DNA ladder occurred in all experimental animals, suggesting that myocardial apoptosis is primarily elicited by R. Densitometrically, Western blot analysis showed significant reduction in expression of Bcl-2 (16 +/- 1%) and increase in Bax (29 +/- 8%) after 6 h R in the necrotic area compared with normal tissue while expression of these two proteins was not changed in the PI group. Polymorphonuclear neutrophil (PMN) accumulation in the necrotic area determined either by immunohistochemistry with anti-CD18 antibody or by myeloperoxidase activity was significantly increased in the I/R group compared to the PI group (358 +/- 24 vs. 24 +/- 2, mm2 myocardium, P < 0.01) and (2.9 +/- 0.3 vs. 0.4 +/- 0.1, U/100 mg tissue, P < 0.01). There was a significant linear relationship between CD18-positive PMNs and TUNEL-positive cells (P < 0.05) in the I/R group.
Conclusions: These results indicate that (1) PI without R did not induce apoptotic cell death, while two types of cell death, necrosis and apoptosis were found after I/R, (2) the Bcl-2 family may participate in early R-induced myocardial apoptosis, (3) PMN accumulation may play a role in the development of apoptosis.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/10728386
Author(s): Suriamoorthy P, Zhang X, Hao G, Joly AG, Singh S, et al.
Author(s): Parveen S, Sahoo SK
Author(s): Smith GL, Shih YC, Giordano SH, Smith BD, Buchholz TA
Author(s): Nel A, Xia T, Mädler L, Li N
Author(s): Seigneuric R, Markey L, Nuyten DS, Dubernet C, Evelo CT, et al.
Author(s): Thorek DL, Chen AK, Czupryna J, Tsourkas A
Author(s): Huang X, Jain PK, El-Sayed IH, El-Sayed MA
Author(s): El-Sayed IH, Huang X, El-Sayed MA
Author(s): Abdelwahed W, Degobert G, Stainmesse S, Fessi H
Author(s): Donaldson K, Aitken R, Tran L, Stone V, Duffin R, et al.
Author(s): Wyllie AH
Author(s): Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, et al.
Author(s): Durand RE
Author(s): Chandran SP, Chaudhary M, Pasricha R, Ahmad A, Sastry M
Author(s): Kasthuri J, Kathiravan K, Rajendiran NJ
Author(s): Shipway AN, Katz E, Willner I
Author(s): Shankar SS, Rai A, Ahmad A, Sastry M
Author(s): Singh M, Kalaivani R, Manikandan S, Sangeetha N, Kumaraguru AK
Author(s): Chen PC, Mwakwari SC, Oyelere AK
Author(s): Gobin AM, Lee MH, Halas NJ, James WD, Drezek RA, et al.
Author(s): Sperling RA, Rivera Gil P, Zhang F, Zanella M, Parak WJ
Author(s): Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, et al.
Author(s): Gavrieli Y, Sherman Y, Ben-Sasson SA
Author(s): Oberhammer F, Wilson JW, Dive C, Morris ID, Hickman JA et al.
Author(s): Aljandali A, Pollack H, Yeldandi A, Li Y, Weitzman SA, et al.
Author(s): Isakovic A, Markovic Z, Todorovic-Markovic B, Nikolic N, Vranjes-Djuric S, et al.
Author(s): Ciapetti G, Granchi D, Savarino L, Cenni E, Magrini E, et al.
Author(s): Allen RT, Hunter WJ 3rd, Agrawal DK