Calpain system and its involvement in myocardial ischemia and reperfusion injury

Neuhof, Christiane

doi:10.4330/wjc.v6.i7.638

Cited by 72 publications

(56 citation statements)

References 207 publications

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“…Microparticle derived PAF may be of particular importance in I/R since this powerful mediator activates platelets to promote their aggregation, adhesion to endothelial cells and leukocytes, and leukocyte sequestration in postischemic tissues. Calpain, a protease implicated in I/R, is also carried on these vesicular structures, which protects the enzyme from plasma inhibitors (413, 584). …”

Section: Plasma Membrane-derived Microparticlesmentioning

confidence: 99%

Ischemia/Reperfusion

Kalogeris

Baines

Krenz

et al. 2016

Comprehensive Physiology

648

565

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Ischemic disorders, such as myocardial infarction, stroke, and peripheral vascular disease, are the most common causes of debilitating disease and death in westernized cultures. The extent of tissue injury relates directly to the extent of blood flow reduction and to the length of the ischemic period, which influence the levels to which cellular ATP and intracellular pH are reduced. By impairing ATPase-dependent ion transport, ischemia causes intracellular and mitochondrial calcium levels to increase (calcium overload). Cell volume regulatory mechanisms are also disrupted by the lack of ATP, which can induce lysis of organelle and plasma membranes. Reperfusion, although required to salvage oxygen-starved tissues, produces paradoxical tissue responses that fuel the production of reactive oxygen species (oxygen paradox), sequestration of proinflammatory immunocytes in ischemic tissues, endoplasmic reticulum stress, and development of postischemic capillary no-reflow, which amplify tissue injury. These pathologic events culminate in opening of mitochondrial permeability transition pores as a common end-effector of ischemia/reperfusion (I/R)-induced cell lysis and death. Emerging concepts include the influence of the intestinal microbiome, fetal programming, epigenetic changes, and microparticles in the pathogenesis of I/R. The overall goal of this review is to describe these and other mechanisms that contribute to I/R injury. Because so many different deleterious events participate in I/R, it is clear that therapeutic approaches will be effective only when multiple pathologic processes are targeted. In addition, the translational significance of I/R research will be enhanced by much wider use of animal models that incorporate the complicating effects of risk factors for cardiovascular disease.

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Section: Plasma Membrane-derived Microparticlesmentioning

confidence: 99%

Ischemia/Reperfusion

Kalogeris

Baines

Krenz

et al. 2016

Comprehensive Physiology

648

565

View full text Add to dashboard Cite

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“…A review (Neuhof and Neuhof, 2014) recently demonstrated that calpain inhibition in animal experiments showed an enhanced tolerance towards ischemia (Neuhof et al , 2003), a reduction of myocardial infarction and reperfusion injury (Hernando et al , 2010; Khalil et al , 2005; Neuhof et al , 2008; Neuhof et al , 2004), and less remodeling (Ma et al , 2012). Other experiments have also shown neuronal preservation during ischemia with calpain inhibition (Nath et al , 2000).…”

Section: Pharmacologic Therapiesmentioning

confidence: 99%

Mitochondrial function in hypoxic ischemic injury and influence of aging

Ham

Raju

2017

Progress in Neurobiology

282

205

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Mitochondria are a major target in hypoxic/ischemic injury. Mitochondrial impairment increases with age leading to dysregulation of molecular pathways linked to mitochondria. The perturbation of mitochondrial homeostasis and cellular energetics worsens outcome following hypoxic-ischemic insults in elderly individuals. In response to acute injury conditions, cellular machinery relies on rapid adaptations by modulating posttranslational modifications. Therefore, post-translational regulation of molecular mediators such as hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), c-MYC, SIRT1 and AMPK play a critical role in the control of the glycolytic-mitochondrial energy axis in response to hypoxic-ischemic conditions. The deficiency of oxygen and nutrients leads to decreased energetic reliance on mitochondria, promoting glycolysis. The combination of pseudohypoxia, declining autophagy, and dysregulation of stress responses with aging adds to impaired host response to hypoxic-ischemic injury. Furthermore, intermitochondrial signal propagation and tissue wide oscillations in mitochondrial metabolism in response to oxidative stress are emerging as vital to cellular energetics. Recently reported intercellular transport of mitochondria through tunneling nanotubes also play a role in the response to and treatments for ischemic injury. In this review we attempt to provide an overview of some of the molecular mechanisms and potential therapies involved in the alteration of cellular energetics with aging and injury with a neurobiological perspective.

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“…Persistent activation of calpain proteases is another mechanism by which persistent hypotension leads to neuronal pathology (123). Calpains cleave the contractile components of vascular smooth muscles inhibiting their ability to contract (122). …”

Section: Chronic Effects Of Traumatic Brain Injurymentioning

confidence: 99%

Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury

Logsdon

Lucke‐Wold

Turner

et al. 2015

Comprehensive Physiology

127

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Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis.

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Calpain system and its involvement in myocardial ischemia and reperfusion injury

Cited by 72 publications

References 207 publications

Ischemia/Reperfusion

Ischemia/Reperfusion

Mitochondrial function in hypoxic ischemic injury and influence of aging

Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury

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