Thyroid hormone in the frontier of cell protection, survival and functional recovery

2015 ◽  
Vol 17 ◽  
Author(s):  
Luis A. Videla ◽  
Virginia Fernández ◽  
Pamela Cornejo ◽  
Romina Vargas ◽  
Iván Castillo
Keyword(s):  
Thyroid Hormone ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Bipolar Disorders ◽  
Nuclear Factor Κb ◽  
Ros Generation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cell Protection ◽  
Beneficial Effects

Thyroid hormone (TH) exerts important actions on cellular energy metabolism, accelerating O2consumption with consequent reactive oxygen species (ROS) generation and redox signalling affording cell protection, a response that is contributed by redox-independent mechanisms. These processes underlie genomic and non-genomic pathways, which are integrated and exhibit hierarchical organisation. ROS production led to the activation of the redox-sensitive transcription factors nuclear factor-κB, signal transducer and activator of transcription 3, activating protein 1 and nuclear factor erythroid 2-related factor 2, promoting cell protection and survival by TH. These features involve enhancement in the homeostatic potential including antioxidant, antiapoptotic, antiinflammatory and cell proliferation responses, besides higher detoxification capabilities and energy supply through AMP-activated protein kinase upregulation. The above aspects constitute the molecular basis for TH-induced preconditioning of the liver that exerts protection against ischemia-reperfusion injury, a strategy also observed in extrahepatic organs of experimental animals and with other types of injury, which awaits application in the clinical setting. Noteworthy, re-adjusting TH to normal levels results in several beneficial effects; for example, it lengthens the cold storage time of organs for transplantation from brain-dead donors; allows a superior neurological outcome in infants of <28 weeks of gestation; reduces the cognitive side-effects of lithium and improves electroconvulsive therapy in patients with bipolar disorders.

scholarly journals Immune‐Responsive Gene 1/Itaconate Activates Nuclear Factor Erythroid 2–Related Factor 2 in Hepatocytes to Protect Against Liver Ischemia–Reperfusion Injury

Hepatology ◽  
2020 ◽  
Vol 72 (4) ◽  
pp. 1394-1411 ◽  
Author(s):  
Zhongjie Yi ◽  
Meihong Deng ◽  
Melanie J. Scott ◽  
Guang Fu ◽  
Patricia A. Loughran ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Liver Ischemia ◽  
Responsive Gene

Attenuation of lung reperfusion injury after transplantation using an inhibitor of nuclear factor-κB

2000 ◽  
Vol 279 (3) ◽  
pp. L528-L536 ◽  
Author(s):  
Scott D. Ross ◽  
Irving L. Kron ◽  
James J. Gangemi ◽  
Kimberly S. Shockey ◽  
Mark Stoler ◽  
...  
Keyword(s):  
Lung Function ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Nuclear Factor Κb ◽  
Pyrrolidine Dithiocarbamate ◽  
Nuclear Factor ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

A central role for nuclear factor-κB (NF-κB) in the induction of lung inflammatory injury is emerging. We hypothesized that NF-κB is a critical early regulator of the inflammatory response in lung ischemia-reperfusion injury, and inhibition of NF-κB activation reduces this injury and improves pulmonary graft function. With use of a porcine transplantation model, left lungs were harvested and stored in cold Euro-Collins preservation solution for 6 h before transplantation. Activation of NF-κB occurred 30 min and 1 h after transplant and declined to near baseline levels after 4 h. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-κB, given to the lung graft during organ preservation (40 mmol/l) effectively inhibited NF-κB activation and significantly improved lung function. Compared with control lungs 4 h after transplant, PDTC-treated lungs displayed significantly higher oxygenation, lower Pco2, reduced mean pulmonary arterial pressure, and reduced edema and cellular infiltration. These results demonstrate that NF-κB is rapidly activated and is associated with poor pulmonary graft function in transplant reperfusion injury, and targeting of NF-κB may be a promising therapy to reduce this injury and improve lung function.

Nuclear factor-κB inhibition by pyrrolidinedithiocarbamate attenuates gastric ischemia-reperfusion injury in rats

2005 ◽  
Vol 83 (6) ◽  
pp. 483-492 ◽  
Author(s):  
Eman El Eter ◽  
Hanan H Hagar ◽  
Ali Al-Tuwaijiri ◽  
Maha Arafa
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Thiobarbituric Acid ◽  
Nuclear Factor Κb ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Nuclear Factor ◽  
P53 Expression ◽  
Apoptotic Protein ◽  
Gastric Ischemia

Pyrrolidinedithiocarbamate (PDTC) is a potent antioxidant and an inhibitor of nuclear factor-κB (NF-κB). The present study examined the impact of PDTC preconditioning on gastric protection in response to ischemia-reperfusion (I/R) injury to the rat stomach. Male Wistar rats were recruited and divided into 3 groups (n=7). One group was subjected to gastric ischemia for 30 min and reperfusion for 1 hour. The second group of rats was preconditioned with PDTC (200 mg/kg body mass i.v.) 15 min prior to ischemia and before reperfusion. The third group of rats was sham-operated and served as the control group. Gastric I/R injury increased serum lactate dehydrogenase level, vascular permeability of gastric mucosa (as indicated by Evans blue dye extravasation) and gastric content of inflammatory cytokine; tumor necrosis factor-α (TNF-α). Moreover, oxidative stress was increased as indicated by elevated lipid peroxides formation (measured as thiobarbituric acid reactive substances) and depleted reduced glutathione in gastric tissues. NF-κB translocation was also detected by electrophoretic mobility shift assay. Microscopically, gastric tissues subjected to I/R injury showed ulceration, hemorrhages, and neutrophil infiltration. Immunohistochemical studies of gastric sections revealed increased expression of p53 and Bcl-2 proteins. PDTC pretreatment reduced Evans blue extravasation, serum lactate dehydrogenase levels, gastric TNF-α levels, and thiobarbituric acid reactive substances content, and increased gastric glutathione content. Moreover, PDTC pretreatment abolished p53 expression and inhibited NF-κB translocation. Finally, histopathological changes were nearly restored by PDTC pretreatment. These results clearly demonstrate that NF-κB activation and pro-apoptotic protein p53 induction are involved in gastric I/R injury. PDTC protects against gastric I/R injury by an antioxidant, NF-κB inhibition, and by reduction of pro-apoptotic protein p53 expression, which seems to be downstream to NF-κB, thus promoting cell survival. Key words: pyrrolidinedithiocarbamate, ischemia–reperfusion injury, gastric mucosa, nuclear factor-κB, inflammatory cytokines, oxidative stress.

Effect of a Novel Nuclear Factor-κB Activation Inhibitor on Renal Ischemia-Reperfusion Injury

2013 ◽  
Vol 96 (10) ◽  
pp. 863-870 ◽  
Author(s):  
Hidaka Kono ◽  
Ken Nakagawa ◽  
Shinya Morita ◽  
Kazunobu Shinoda ◽  
Ryuichi Mizuno ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nuclear Factor Κb ◽  
Renal Ischemia ◽  
Nuclear Factor ◽  
Renal Ischemia Reperfusion Injury

scholarly journals Electron leak from NDUFA13 within mitochondrial complex I attenuates ischemia-reperfusion injury via dimerized STAT3

2017 ◽  
Vol 114 (45) ◽  
pp. 11908-11913 ◽  
Author(s):  
Hengxun Hu ◽  
Jinliang Nan ◽  
Yong Sun ◽  
Dan Zhu ◽  
Changchen Xiao ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Oxygen Consumption ◽  
Complex I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Cell Protection ◽  
Causative Relationship ◽  
R Process ◽  
And Function

The causative relationship between specific mitochondrial molecular structure and reactive oxygen species (ROS) generation has attracted much attention. NDUFA13 is a newly identified accessory subunit of mitochondria complex I with a unique molecular structure and a location that is very close to the subunits of complex I of low electrochemical potentials. It has been reported that down-regulated NDUFA13 rendered tumor cells more resistant to apoptosis. Thus, this molecule might provide an ideal opportunity for us to investigate the profile of ROS generation and its role in cell protection against apoptosis. In the present study, we generated cardiac-specific tamoxifen-inducible NDUFA13 knockout mice and demonstrated that cardiac-specific heterozygous knockout (cHet) mice exhibited normal cardiac morphology and function in the basal state but were more resistant to apoptosis when exposed to ischemia-reperfusion (I/R) injury. cHet mice showed a preserved capacity of oxygen consumption rate by complex I and II, which can match the oxygen consumption driven by electron donors ofN,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD)+ascorbate. Interestingly, at basal state, cHet mice exhibited a higher H2O2level in the cytosol, but not in the mitochondria. Importantly, increased H2O2served as a second messenger and led to the STAT3 dimerization and, hence, activation of antiapoptotic signaling, which eventually significantly suppressed the superoxide burst and decreased the infarct size during the I/R process in cHet mice.

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