Modification of Ischemia/Reperfusion-Induced Alterations in Subcellular Organelles by Ischemic Preconditioning

Tappia, Paramjit S.; Shah, Anureet K.; Ramjiawan, Bram; Dhalla, Naranjan S.

doi:10.3390/ijms23073425

Cited by 14 publications

(16 citation statements)

References 214 publications

(251 reference statements)

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“…In order to attenuate the adverse effects of oxidative/nitrosative stress, inflammation and intracellular Ca 2+ -overload in I/R hearts, different redox-based strategies involving endogenous components have been attempted to prevent I/R-induced myocardial cell damage and cardiac dysfunction [ 77 , 78 , 79 ]. Particularly, interventions such as ischemic preconditioning, ischemic postconditioning, and remote conditioning have been demonstrated to exert cardioprotective actions in improving cardiac performance as well as limiting infarct size and preventing adverse cardiac remodeling due to I/R injury [ 80 , 81 , 82 ]. It is pointed out that there are several other conditions such as hibernation of myocardium and early stages of myocardial ischemia but their cardioprotective effects against I/R injury have not been examined in details.…”

Section: Cardioprotection In Hearts Subjected To I/r Injurymentioning

confidence: 99%

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

et al. 2022

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Ischemia-reperfusion (I/R) injury is well-known to be associated with impaired cardiac function, massive arrhythmias, marked alterations in cardiac metabolism and irreversible ultrastructural changes in the heart. Two major mechanisms namely oxidative stress and intracellular Ca2+-overload are considered to explain I/R-induced injury to the heart. However, it is becoming apparent that oxidative stress is the most critical pathogenic factor because it produces myocardial abnormalities directly or indirectly for the occurrence of cardiac damage. Furthermore, I/R injury has been shown to generate oxidative stress by promoting the formation of different reactive oxygen species due to defects in mitochondrial function and depressions in both endogenous antioxidant levels as well as regulatory antioxidative defense systems. It has also been demonstrated to adversely affect a wide variety of metabolic pathways and targets in cardiomyocytes, various resident structures in myocardial interstitium, as well as circulating neutrophils and leukocytes. These I/R-induced alterations in addition to myocardial inflammation may cause cell death, fibrosis, inflammation, Ca2+-handling abnormalities, activation of proteases and phospholipases, as well as subcellular remodeling and depletion of energy stores in the heart. Analysis of results from isolated hearts perfused with or without some antioxidant treatments before subjecting to I/R injury has indicated that cardiac dysfunction is associated with the development of oxidative stress, intracellular Ca2+-overload and protease activation. In addition, changes in the sarcolemma and sarcoplasmic reticulum Ca2+-handling, mitochondrial oxidative phosphorylation as well as myofibrillar Ca2+-ATPase activities in I/R hearts were attenuated by pretreatment with antioxidants. The I/R-induced alterations in cardiac function were simulated upon perfusing the hearts with oxyradical generating system or oxidant. These observations support the view that oxidative stress may be intimately involved in inducing intracellular Ca2+-overload, protease activation, subcellular remodeling, and cardiac dysfunction as a consequence of I/R injury to the heart.

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Section: Cardioprotection In Hearts Subjected To I/r Injurymentioning

confidence: 99%

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

et al. 2022

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“…Indeed, our previous studies found that high doses of NE could further induce mitochondrial fragmentation by disrupting actin. Some studies also showed that sustained high NE levels led to decreased mitochondrial calcium uptake and increased intracytoplasmic calcium concentration ( Gutiérrez et al, 2014 ), then the communication and proximity between SR/ER and mitochondria were changed ( Tappia et al, 2022 ). That may be the reason why 0.5 μg/kg/min did not significantly attenuate mitochondrial damage induced by UHS.…”

Section: Discussionmentioning

confidence: 99%

Low-dose norepinephrine in combination with hypotensive resuscitation may prolong the golden window for uncontrolled hemorrhagic shock in rats

Zhou

Li²,

Xiang³

et al. 2022

Front. Physiol.

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Hypotension resuscitation is an important principle for the treatment after trauma. Current hypotensive resuscitation strategies cannot obtain an ideal outcome for remote regions. With the uncontrolled hemorrhagic shock (UHS) model in rats, the effects of norepinephrine (NE) on the tolerance time of hypotensive resuscitation, blood loss, vital organ functions, and animal survival were observed. Before bleeding was controlled, only the LR infusion could effectively maintain the MAP to 50–60 mmHg for 1 h, while the MAP gradually decreased with prolonging time, even with increasing infusion volume. Low-dose NE during hypotensive resuscitation prolonged the hypotensive tolerance time to 2–3 h, and the effect of 0.3 μg/kg/min NE was the best. Further studies showed that 0.3 μg/kg/min NE during hypotensive resuscitation significantly lightened the damage of organ function induced by UHS via protecting mitochondrial function, while the LR infusion did not. At the same time, NE administration improved Hb content, DO2, and VO2, and restored liver and kidney blood flow. The survival results showed that low-dose NE administration increased the survival rate and prolonged the survival time. Together, low-dose NE during hypotensive resuscitation was suitable for the early treatment of UHS, which can strive for the golden window of emergency treatment for serious trauma patients by reducing blood loss and protecting vital organ functions.

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“…IPC is con rmed to be a safe and e cient method with potential protective effect on organs recently [22].…”

Section: Discussionmentioning

confidence: 99%

Ischemic preconditioning attenuates ERS-dependent apoptosis of hepatocyte through regulating autophagy in hepatic ischemia reperfusion injury

Kong

Geng

et al. 2022

Preprint

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Hepatic ischemia reperfusion injury (HIRI) usually occurs in subtotal hepatectomy and severely damages liver function during perioperative period. Endoplasmic reticulum stress (ERS) dependent apoptosis was suggested to crucially participate in the progression of HIRI. The present study focused on the regulatory effect of autophagy activation induced by ischemic preconditioning (IPC) on ERS-dependent apoptosis of hepatocyte in HIRI. HIRI mice model and oxygen glucose deprivation/reperfusion (OGD/R) AML-12 hepatocyte cell lines were both constructed to evaluate the protective effect of IPC in vivo and in vitro, separately. The protein levels of p-eIF2α, CHOP, cleaved caspase-12 were used to evaluate the ERS-dependent apoptosis, while LC3-II and p62 were regarded as the autophagy activation markers. The beneficial molecular chaperones GRP78, HSP60, HSP70 were also tested to evaluate autophagy. The results showed that HIRI significantly increased the ERS-dependent apoptosis markers and the number of apoptotic cells, and damaged liver function. The ERS inhibitor Salubrinal (Sal) intraperitoneally greatly alleviated liver injury in HIRI mice and OGD/R hepatocytes. Further, both remote IPC (RIPC) and direct IPC (DIPC) significantly alleviated liver injury and inflammatory cell infiltration. IPC also up-regulated LC3-II and down-regulated p62 expression, and increased the mRNA levels of GRP78, HSP60, HSP70 in HIRI mice and OGD/R hepatocytes, indicating the autophagy activation by IPC. Autophagy inhibitor 3-methyladenine (3-MA) significantly attenuated the protective effects of IPC on ERS-dependent apoptosis and liver function, while autophagy activator rapamycin (RAP) mimicked the protective effects of IPC on ERS-dependent apoptosis in vitro, suggesting the regulatory roles of autophagy on ERS-dependent apoptosis. These results all demonstrated that IPC could induce moderate autophagy and up-regulate some molecular chaperones to strengthen the endogenous defense mechanisms, which was beneficial to alleviate ERS-dependent apoptosis and protect hepatocytes from HIRI.

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Modification of Ischemia/Reperfusion-Induced Alterations in Subcellular Organelles by Ischemic Preconditioning

Cited by 14 publications

References 214 publications

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

Low-dose norepinephrine in combination with hypotensive resuscitation may prolong the golden window for uncontrolled hemorrhagic shock in rats

Ischemic preconditioning attenuates ERS-dependent apoptosis of hepatocyte through regulating autophagy in hepatic ischemia reperfusion injury

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