Ischemic preconditioning.

E R Schwarz; W S Whyte; R A Kloner

Home/Archive/PubMed

PubMed · 9352175

Ischemic preconditioning.

E R Schwarz·W S Whyte·R A Kloner

View original source ↗Export metadata ↓

Abstract

It has been shown that repeated brief coronary occlusions increase myocardial resistance towards prolonged episodes of ischemia. This phenomenon, which renders the heart more tolerant to ischemia with subsequent limitation of infarct size, has been termed ischemic preconditioning and has been described in a variety of species. Preconditioning may also protect the heart against postischemic dysfunction and ventricular arrhythmias. Although the beneficial effects seem to be transient, they re-appear at 24 hours, representing a "second window of protection." Ischemia-induced activation of adenosine receptors and opening of ATP-sensitive potassium channels appear to play a role in the acute cardioprotection. For the late protection, stress protein synthesis may play a role. There is experimental and clinical evidence that preconditioning effects may also exist in the human heart. If so, the mechanisms of ischemic preconditioning might be applied to future therapy.

Explore related subjects

Adenosine Triphosphate Animals Heat-Shock Proteins Humans Ischemic Preconditioning, Myocardial Myocardial Ischemia Potassium Channels Receptors, Purinergic P1 Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

E R Schwarz, W S Whyte, R A Kloner. 1997. Ischemic preconditioning.. https://pubmed.ncbi.nlm.nih.gov/9352175/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2022

The human mitochondrial genome contains a second light strand promoter.

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.

Adenosine Triphosphate↗

PubMed2021

GCN2 kinase activation by ATP-competitive kinase inhibitors.

Small-molecule kinase inhibitors represent a major group of cancer therapeutics, but tumor responses are often incomplete. To identify pathways that modulate kinase inhibitor response, we conducted a genome-wide knockout (KO) screen in glioblastoma cells treated with the pan-ErbB inhibitor neratinib. Loss of general control nonderepressible 2 (GCN2) kinase rendered cells resistant to neratinib, whereas depletion of the GADD34 phosphatase increased neratinib sensitivity. Loss of GCN2 conferred neratinib resistance by preventing binding and activation of GCN2 by neratinib. Several other Food and Drug Administration (FDA)-approved inhibitors, such erlotinib and sunitinib, also bound and activated GCN2. Our results highlight the utility of genome-wide functional screens to uncover novel mechanisms of drug action and document the role of the integrated stress response (ISR) in modulating the response to inhibitors of oncogenic kinases.

Adenosine Triphosphate↗

PubMed1999

Role of Suc1 in the activation of the cyclosome by protein kinase Cdk1/cyclin B.

A large complex, called the cyclosome or anaphase-promoting complex, has specific and regulated protein-ubiquitin ligase activity that targets mitotic regulators (such as cyclin B) for degradation at the end of mitosis. In early embryonic cell cycles the cyclosome is inactive in the interphase, but is subsequently converted by protein kinase Cdk1/cyclin B to an active, phosphorylated form, in a process that includes an initial lag period. This time lag may be important to prevent premature self-inactivation of Cdk1/cyclin B before the end of mitosis. We have previously observed that the phosphorylated form of the cyclosome binds to Suc1, a protein that associates with Cdk1 and with phosphate-containing compounds. We now report that low, physiological concentrations of Suc1 stimulate the activation of the interphase form of the cyclosome by the protein kinase. When Suc1 was present from the beginning of the incubation together with protein kinase Cdk1/cyclin B, activation of the cyclosome took place with the normal lag kinetics. However, when interphase cyclosome was first incubated with protein kinase Cdk1/cyclin B without Suc1, the subsequent addition of Suc1 caused a rapid burst of cyclosome activation and the lag was completely abolished. These findings are consistent with the interpretation that following initial slow phosphorylations of the cyclosome by the protein kinase, Suc1 accelerates multiple phosphorylations that culminate in the full activation of the cyclosome. In support of this interpretation, we find that Suc1 stimulates the phosphorylation of several proteins in the preparation of interphase cyclosome and that the effect of Suc1 on phosphorylation was augmented by prior incubation of interphase cyclosome with protein kinase Cdk1/cyclin B.

Adenosine Triphosphate↗