scholarly journals The Commonalities and Differences in Mitochondrial Dysfunction Between ex vivo and in vivo Myocardial Global Ischemia Rat Heart Models: Implications for Donation After Circulatory Death Research

2020 ◽  
Vol 11 ◽  
Author(s):  
Mohammed Quader ◽  
Oluwatoyin Akande ◽  
Stefano Toldo ◽  
Renee Cholyway ◽  
Le Kang ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Rat Heart ◽  
Ex Vivo ◽  
Global Ischemia ◽  
Donation After Circulatory Death ◽  
Circulatory Death

scholarly journals Insulin Resistance Promotes Parkinson’s Disease through Aberrant Expression of α-Synuclein, Mitochondrial Dysfunction, and Deregulation of the Polo-Like Kinase 2 Signaling

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 740 ◽  
Author(s):  
Chien-Tai Hong ◽  
Kai-Yun Chen ◽  
Weu Wang ◽  
Jing-Yuan Chiu ◽  
Dean Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Ex Vivo ◽  
Proteinase K ◽  
Ros Production ◽  
Aberrant Expression ◽  
In Vivo Models

Background: Insulin resistance (IR), considered a hallmark of diabetes at the cellular level, is implicated in pre-diabetes, results in type 2 diabetes, and negatively affects mitochondrial function. Diabetes is increasingly associated with enhanced risk of developing Parkinson’s disease (PD); however, the underlying mechanism remains unclear. This study investigated the probable culpability of IR in the pathogenesis of PD. Methods: Using MitoPark mice in vivo models, diabetes was induced by a high-fat diet in the in vivo models, and IR was induced by protracted pulse-stimulation with 100 nM insulin treatment of neuronal cells, in vitro to determine the molecular mechanism(s) underlying altered cellular functions in PD, including mitochondrial dysfunction and α-synuclein (SNCA) aberrant expression. Findings: We observed increased SNCA expression in the dopaminergic (DA) neurons of both the wild-type and diabetic MitoPark mice, coupled with enhanced degeneration of DA neurons in the diabetic MitoPark mice. Ex vivo, in differentiated human DA neurons, IR was associated with increased SNCA and reactive oxygen species (ROS) levels, as well as mitochondrial depolarization. Moreover, we demonstrated concomitant hyperactivation of polo-like kinase-2 (PLK2), and upregulated p-SNCA (Ser129) and proteinase K-resistant SNCA proteins level in IR SH-SY5Y cells, however the inhibition of PLK2 reversed IR-related increases in phosphorylated and total SNCA. Similarly, the overexpression of peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC)-1α suppressed ROS production, repressed PLK2 hyperactivity, and resulted in downregulation of total and Ser129-phosphorylated SNCA in the IR SH-SY5Y cells. Conclusions: These findings demonstrate that IR-associated diabetes promotes the development and progression of PD through PLK2-mediated mitochondrial dysfunction, upregulated ROS production, and enhanced SNCA signaling, suggesting the therapeutic targetability of PLK2 and/or SNCA as potential novel disease-modifying strategies in patients with PD.

Donation after Brain Death versus Donation after Circulatory Death: Lung Donor Management Issues

2018 ◽  
Vol 39 (02) ◽  
pp. 138-147 ◽  
Author(s):  
Bronwyn Levvey ◽  
Kovi Levin ◽  
Miranda Paraskeva ◽  
Glen Westall ◽  
Gregory Snell
Keyword(s):  
Brain Death ◽  
Ex Vivo ◽  
Scoring Systems ◽  
Donation After Circulatory Death ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Conversion Rates ◽  
Donor Lung ◽  
Donation After Brain Death ◽  
Circulatory Death

AbstractLung transplantation (LTx) has traditionally been limited by a lack of suitable donor lungs. With the recognition that lungs are more robust than initially thought, the size of the donor pool of available lungs has increased dramatically in the past decade. Donation after brain death (DBD) and donation after circulatory death (DCD) lungs, both ideal and extended are now routinely utilized. DBD lungs can be damaged. There are important differences in the public's understanding, legal and consent processes, intensive care unit strategies, lung pathophysiology, logistics, and potential-to-actual donor conversion rates between DBD and DCD. Notwithstanding, the short- and long-term outcomes of LTx from any of these DBD versus DCD donor scenarios are now similar, robust, and continue to improve. Large audits suggest there remains a large untapped pool of DCD (but not DBD) lungs that may yet further dramatically increase lung transplant numbers. Donor scoring systems that might predict the donor conversion rates and lung quality, the role of ex vivo lung perfusion as an assessment and lung resuscitation tool, as well as the potential of donor lung quality biomarkers all have immense promise for the clinical field.

scholarly journals Donation After Circulatory Death Lungs Transplantable Up to Six Hours After Ex Vivo Lung Perfusion

2016 ◽  
Vol 102 (6) ◽  
pp. 1845-1853 ◽  
Author(s):  
Eric J. Charles ◽  
Mary E. Huerter ◽  
Cynthia E. Wagner ◽  
Ashish K. Sharma ◽  
Yunge Zhao ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Lung Perfusion ◽  
Donation After Circulatory Death ◽  
Ex Vivo Lung Perfusion ◽  
Circulatory Death

Flow-targeted pediatric ex vivo heart perfusion in donation after circulatory death: A porcine model

2020 ◽  
Vol 39 (3) ◽  
pp. 267-277
Author(s):  
Junko Kobayashi ◽  
Shuhua Luo ◽  
Yohei Akazawa ◽  
Marlee Parker ◽  
Jian Wang ◽  
...  
Keyword(s):  
Porcine Model ◽  
Ex Vivo ◽  
Donation After Circulatory Death ◽  
Heart Perfusion ◽  
Circulatory Death

scholarly journals Development of an ex vivo technique to achieve reanimation of hearts sourced from a porcine donation after circulatory death model

2014 ◽  
Vol 189 (2) ◽  
pp. 326-334 ◽  
Author(s):  
Omar A. Mownah ◽  
Muhammad A. Khurram ◽  
Christopher Ray ◽  
Aditya Kanwar ◽  
Susan Stamp ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Donation After Circulatory Death ◽  
Circulatory Death

Carnitine supplementation in high-fat diet-fed rats does not ameliorate lipid-induced skeletal muscle mitochondrial dysfunction in vivo

2015 ◽  
Vol 309 (7) ◽  
pp. E670-E678 ◽  
Author(s):  
Bart Wessels ◽  
Nicole M. A. van den Broek ◽  
Jolita Ciapaite ◽  
Sander M. Houten ◽  
Ronald J. A. Wanders ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Carnitine Supplementation ◽  
High Fat ◽  
Muscle Lipid ◽  
Lipid Status

Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid intermediates out of the mitochondria. The aim of the present study was to test the hypothesis that carnitine supplementation reduces high-fat diet-induced lipotoxicity, improves muscle mitochondrial function, and ameliorates insulin resistance. Wistar rats were fed either normal chow or a high-fat diet for 15 wk. One group of high-fat diet-fed rats was supplemented with 300 mg·kg−1·day−1 l-carnitine during the last 8 wk. Muscle mitochondrial function was measured in vivo by 31P magnetic resonance spectroscopy (MRS) and ex vivo by high-resolution respirometry. Muscle lipid status was determined by 1H MRS (intramyocellular lipids) and tandem mass spectrometry (acylcarnitines). High-fat diet feeding induced insulin resistance and was associated with decreases in muscle and blood free carnitine, elevated levels of muscle lipids and acylcarnitines, and an increased number of muscle mitochondria that showed an improved capacity to oxidize fat-derived substrates when tested ex vivo. This was, however, not accompanied by an increase in muscle oxidative capacity in vivo, indicating that in vivo mitochondrial function was compromised. Despite partial normalization of muscle and blood free carnitine content, carnitine supplementation did not induce improvements in muscle lipid status, in vivo mitochondrial function, or insulin sensitivity. Carnitine insufficiency, therefore, does not play a major role in high-fat diet-induced muscle mitochondrial dysfunction in vivo.

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