Nicorandil decreases postischemic actin oxidation

Schwalb, Herzl; Olivson, A.; Li, Judy; Houminer, Esther; Wahezi, Sayed E.; Opie, Lionel H.; Maulik, Dev; Borman, Joseph B.; Powell, Saul R.

doi:10.1016/s0891-5849(01)00620-7

Cited by 19 publications

(14 citation statements)

References 38 publications

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“…Protein carbonyls were then determined using an immunoblot technique and antibody specific for dinitrophenylhydrazine as previously described (44).…”

Section: Protein Oxidationmentioning

confidence: 99%

“…Myocardial ischemia is associated with numerous posttranslational modifications of proteins, many of which can be ascribed to oxidative phenomena. Indeed, we have demonstrated carbonylation of actin isoforms in the ischemic heart (35,44), and examination of modifications of troponins and other myofilament elements is an ongoing area of research (49). One consequence of protein oxidation is increased vulnerability to proteolysis (14), and both actin and the troponins, and other myofilament elements, are lost following ischemia (16), although the role of the proteasome has not been examined.…”

Section: Introductionmentioning

confidence: 99%

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Oxidized and Ubiquitinated Proteins May Predict Recovery of Postischemic Cardiac Function: Essential Role of the Proteasome

Powell

Wang²,

Katzeff³

et al. 2005

Antioxidants & Redox Signaling

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117

103

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This study examined the hypothesis that postischemic levels of oxidized and/or ubiquitinated proteins may be predictive of functional recovery as they may be indicative of activity of the 20S and/or 26S proteasomes, respectively. Subjecting isolated rat hearts to 15 min of ischemia had no effect on 20S- and 26S-proteasome activities; however, both were significantly (p < 0.05) decreased by 70% and 54%, respectively, following 30 min of ischemia and 60 min of reperfusion, changes associated with increased levels of protein carbonyls and ubiquitinated proteins. Preischemic treatment of hearts with the proteasome inhibitor, MG132, resulted in dose-dependent decreases (p < 0.05) in recovery of postischemic function [MG132 (microM), heart rate x pressure product: 0, 11,158 +/- 2,423; 6, 11,400 +/- 3,009; 12, 5,513 +/- 2,225; 25, 2,325 +/- 992] and increased accumulation of ubiquitinated proteins. Preconditioning with repetitive ischemia (IP) or preischemic treatment with nicorandil (Nic) resulted in a significant increase in postischemic 20S-proteasome activity after 60 min of reperfusion (control, 95 +/- 4; IP, 301 +/- 65; Nic, 242 +/- 61 fluorescence units). Only Nic had similar effects on 26S-proteasome activity. These results support the conclusion that a correlation exists between eventual recovery of postischemic function and levels of oxidized and/or ubiquitinated proteins, a phenomenon that may be dependent on activity of the 20S and 26S proteasomes.

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“…Protein carbonyls were then determined using an immunoblot technique and antibody specific for dinitrophenylhydrazine as previously described (44).…”

Section: Protein Oxidationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxidized and Ubiquitinated Proteins May Predict Recovery of Postischemic Cardiac Function: Essential Role of the Proteasome

Powell

Wang²,

Katzeff³

et al. 2005

Antioxidants & Redox Signaling

Self Cite

117

103

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“…In addition, carbonyl groups may be introduced into proteins by reactions with aldehydes produced during lipid peroxydation [27], or with reactive carbonyl derivatives (ketoamines, ketoaldehydes, deoxyosones) generated as a consequence of the reaction of reducing sugars of their oxidation products with lysine residues of proteins [28]. Therefore, an increase in carbonyl groups indicates enhanced hydroxyl radical-mediated oxidative injury to the protein [29]. In contrast, attenuation of protein oxidation is attributed to inhibition of postischemic OH production.…”

Section: Discussionmentioning

confidence: 99%

Dexrazoxane Prevents Myocardial Ischemia/Reperfusion-Induced Oxidative Stress in the Rat Heart

Ramu

Korach

Houminer

et al. 2006

Cardiovasc Drugs Ther

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“…The observation that fasudil does not affect the recovery of cardiac function during reperfusion in the absence of pinacidil, suggests three possible schemes of interaction between rhoA/ROCK and pinacidil-induced cardioprotection. Pinacidil may activate rhoA/ROCK signaling or protect the rhoA/ROCK signaling pathway from oxidative (5,18) or proteolytic (11) damage during ischemia-reperfusion as part of the cardioprotective process. Alternatively, K ATP channel activation itself may depend on rhoA/ROCK signaling (8).…”

Section: Discussionmentioning

confidence: 99%

Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery

Nishizawa¹,

Wolkowicz²,

Yamagishi

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.

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Nicorandil decreases postischemic actin oxidation

Cited by 19 publications

References 38 publications

Oxidized and Ubiquitinated Proteins May Predict Recovery of Postischemic Cardiac Function: Essential Role of the Proteasome

Oxidized and Ubiquitinated Proteins May Predict Recovery of Postischemic Cardiac Function: Essential Role of the Proteasome

Dexrazoxane Prevents Myocardial Ischemia/Reperfusion-Induced Oxidative Stress in the Rat Heart

Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery

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Nicorandil decreases postischemic actin oxidation

Cited by 19 publications

References 38 publications

Oxidized and Ubiquitinated Proteins May Predict Recovery of Postischemic Cardiac Function: Essential Role of the Proteasome

Oxidized and Ubiquitinated Proteins May Predict Recovery of Postischemic Cardiac Function: Essential Role of the Proteasome

Dexrazoxane Prevents Myocardial Ischemia/Reperfusion-Induced Oxidative Stress in the Rat Heart

Fasudil prevents KATP channel-induced improvement in postischemic functional recovery

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Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery