Impact of Ischemia on Cellular Metabolism

Gourdin, Maximilien; Dubois, Philippe

doi:10.5772/54509

Cited by 16 publications

(20 citation statements)

References 68 publications

(47 reference statements)

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“…This observation might be due to the fact that cells continue protein synthesis under ischemic conditions. Consequently, proteins are generated that adapt cells to ischemic stress conditions, including heat shock proteins (HSPs), and proteins involved in glucose metabolism are newly synthesized [ 20 ] .…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Potential Marker of Tissue Quality Using Gene Expression Analysis of Human Colorectal Tissue

Lange¹,

Unger²,

Schöppler³

et al. 2015

PLoS ONE

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Correlative studies have identified numerous biomarkers that are individualizing therapy across many medical specialties, including oncology. Accurate interpretation of these studies requires the collection of tissue samples of sufficient quality. Tissue quality can be measured by changes in levels of gene expression and can be influenced by many factors including pre-analytical conditions, ischemic effects and the surgical collection procedure itself. However, as yet there are no reliable biomarkers of tissue quality at researchers’ disposal. The aim of the current study was to identify genes with expression patterns that fluctuated reproducibly in response to typical post-surgical stress (ischemia) in order to identify a specific marker of tissue quality. All tissue samples were obtained from patients with primary colorectal carcinoma (CRC) (N = 40) either via colonoscopy prior to surgery, or by surgical resection. Surgically resected tissue samples were divided into three groups and subjected to cold ischemia for 10, 20 or 45 minutes. Normal colorectal tissue and CRC tissue was analyzed using microarray and quantitative real-time PCR (qPCR). Comparing changes in gene expression between pre- and post-surgical tissue using microarray analysis identified a list of potential tissue quality biomarkers and this list was validated using qPCR. Results revealed that post-operative ischemia significantly alters gene expression in normal and CRC tissue samples. Both microarray analysis and qPCR revealed regulator of G-protein signaling 1 (RGS1) as a potential marker of CRC tissue quality and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) as a potential reference gene of post-operative tissue quality. Larger studies with additional time points and endpoints will be needed to confirm these results.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Potential Marker of Tissue Quality Using Gene Expression Analysis of Human Colorectal Tissue

Lange¹,

Unger²,

Schöppler³

et al. 2015

PLoS ONE

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show abstract

“…Hambatan aliran darah yang terjadi di jaringan menyebabkan suplai oksigen terganggu dan mengacaukan reaksi biokimia yang menjamin tetap berlangsungnya fungsi, integritas dan daya tahan selsel. 7 Kondisi iskemia yang berat dan berlangsung lama menyebabkan perubahanperubahan pada tingkat seluler. 7 Terjadi perubahan metabolisme yang berkaitan fosfolipid, peroksidasi lipid, dan kerusakan sitoskeletal (gambar 1).…”

Section: Dampak Iskemia Miokard Pada Metabolisme Selunclassified

“…7 Kondisi iskemia yang berat dan berlangsung lama menyebabkan perubahanperubahan pada tingkat seluler. 7 Terjadi perubahan metabolisme yang berkaitan fosfolipid, peroksidasi lipid, dan kerusakan sitoskeletal (gambar 1). 8,9 Sintesis protein merupakan proses kompleks yang memerlukan asupan energi yang terus menerus dan memadai, kontrol ketat homeostasis ion sel dan kelancaran fungsi banyak protein lainnya.…”

Section: Dampak Iskemia Miokard Pada Metabolisme Selunclassified

“…19 Kenaikan kalsium pada mitokondria akan meningkatkan produksi ROS dan mengurangi kapasitas antioksidan mitokondria dengan menurunnya aktivitas SOD dan konsentrasi glutation peroksidase, yang merupakan sumber utama detoksifikasi terhadap H 2 O 2 . 7,18,19 Semua proses tersebut dapat merusak struktur miokard sehingga terjadi kondisi kardiomiopati yang mengganggu fungsi jantung. 18…”

Section: Peran Radikal Bebas Pada Iskemia Miokardunclassified

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Metabolism changes and the role of the free radicals on myocardial ischemia

Sarvasti

2016

IJC

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Myocardial ischemic results from severe impairment of coronary blood supply and produces a spectrum of clinical syndromes. It results in a characteristic pattern of metabolic and structural changes that leads to extremely complex situations, which have been extensively studied in recent years. A detailed understanding is now available of the complexity of the response of the myocardium to an ischemic insult. Reperfusion is the most effective way to treat the ischaemic myocardial. But, restoration of flow, however, might result in numerous other negative consequences, thus directly influencing the degree of recovery. Much evidence shows that during the period of myocardial ischemia and reperfusion can occur various changes both in terms of metabolic, electrical, histology, structural, and physiological. Pathological changes in the form of metabolic changes and the role of free radicals on the condition of ischemia and reperfusion injury will be discussed. There are several potential manifestations and outcomes associated with myocardial ischemia and reperfusion.

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“…① During ischemia, the deficiency in oxygen and nutrient supply to hepatocytes impairs oxidative degradation of glucose and fatty acids (FAs), which decreases ATP synthesis. The switch to anaerobic metabolism further intensifies ATP depletion and increases lactate formation resulting in metabolic acidosis [ 26 ]. Here, cyclic adenosine monophosphate (cAMP), which is a key second messenger controlling cellular metabolism [ 27 ], is affected during ischemia [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Computational Modeling of Oxidative Stress in Fatty Livers Elucidates the Underlying Mechanism of the Increased Susceptibility to Ischemia/Reperfusion Injury

Schleicher

Dahmen

2018

Computational and Structural Biotechnology Journal

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QuestionDonor liver organs with moderate to high fat content (i.e. steatosis) suffer from an enhanced susceptibility to ischemia/reperfusion injury (IRI) during liver transplantation. Responsible for the cellular injury is an increased level of oxidative stress, however the underlying mechanistic network is still not fully understood.MethodWe developed a phenomenological mathematical model of key processes of hepatic lipid metabolism linked to pathways of oxidative stress. The model allows the simulation of hypoxia (i.e. ischemia-like conditions) and reoxygenation (i.e. reperfusion-like conditions) for various degrees of steatosis and predicts the level of hepatic lipid peroxidation (LPO) as a marker of cell damage caused by oxidative stress.Results & ConclusionsOur modeling results show that the underlying feedback loop between the formation of reactive oxygen species (ROS) and LPO leads to bistable systems behavior. Here, the first stable state corresponds to a low basal level of ROS production. The system is directed to this state for healthy, non-steatotic livers. The second stable state corresponds to a high level of oxidative stress with an enhanced formation of ROS and LPO. This state is reached, if steatotic livers with a high fat content undergo a hypoxic phase. Theoretically, our proposed mechanistic network would support the prediction of the maximal tolerable ischemia time for steatotic livers: Exceeding this limit during the transplantation process would lead to severe IRI and a considerable increased risk for liver failure.

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Impact of Ischemia on Cellular Metabolism

Cited by 16 publications

References 68 publications

Identification and Validation of a Potential Marker of Tissue Quality Using Gene Expression Analysis of Human Colorectal Tissue

Identification and Validation of a Potential Marker of Tissue Quality Using Gene Expression Analysis of Human Colorectal Tissue

Metabolism changes and the role of the free radicals on myocardial ischemia

Computational Modeling of Oxidative Stress in Fatty Livers Elucidates the Underlying Mechanism of the Increased Susceptibility to Ischemia/Reperfusion Injury

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