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Mitochondria AND pain

Michel van Schaardenburgh, Martin Wohlwend, Øivind Rognmo, Erney J R Mattsson
PURPOSE: Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease...
2016: PloS One
Stephen P Dzul, Agostinho G Rocha, Swati Rawat, Ashoka Kandegedara, April Kusowski, Jayashree Pain, Anjaneyulu Murari, Debkumar Pain, Andrew Dancis, Timothy L Stemmler
FeS-clusters are utilized by numerous proteins within several biological pathways that are essential for life. In eukaryotes, the primary FeS-cluster production pathway is the mitochondrial iron-sulfur cluster (ISC) pathway. In Saccharomyces cerevisiae, de novo FeS-cluster formation is accomplished through coordinated assembly with the substrates iron and sulfur by the scaffold assembly protein "Isu1". Sulfur for cluster assembly is provided by cysteine desulfurase "Nfs1", a protein that works in union with its accessory protein "Isd11"...
October 14, 2016: Metallomics: Integrated Biometal Science
Carl M Hurt, Yao Lu, Creed M Stary, Honit Piplani, Bryce A Small, Travis J Urban, Nir Qvit, Garrett J Gross, Daria Mochly-Rosen, Eric R Gross
BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) mediates cellular responses to pain, heat, or noxious stimuli by calcium influx; however, the cellular localization and function of TRPV1 in the cardiomyocyte is largely unknown. We studied whether myocardial injury is regulated by TRPV1 and whether we could mitigate reperfusion injury by limiting the calcineurin interaction with TRPV1. METHODS AND RESULTS: In primary cardiomyocytes, confocal and electron microscopy demonstrates that TRPV1 is localized to the mitochondria...
2016: Journal of the American Heart Association
Hai Xiao, Tingyu Wen, Xinzheng Liu
BACKGROUND: Oncocytic carcinoma (OC) arising in the submandibular gland is an unusual malignant neoplasm, with <20 cases previously reported. The cancer is characterized by numerous morphologically abnormal mitochondria present in the cytoplasm and marked cellular pleomorphism. At its most severe, the tumor may invade into the surrounding tissues, including intravascular, lymphatic, or perineural invasion, and lead to regional nodal or distant metastasis. METHODS: The current study describes a novel OC case in a 46-year-old male, the youngest case of the review...
September 2016: Medicine (Baltimore)
Rodolfo Melaré, Rafael Stuani Floriano, Marta Gracia, Léa Rodrigues-Simioni, Maria Alice da Cruz-Höfling, Thalita Rocha
Bites by Bothrops snakes normally induce local pain, haemorrhage, oedema and myonecrosis. Mammalian isolated nerve-muscle preparations exposed to Bothrops venoms and their phospholipase A2 toxins (PLA2 ) can exhibit a neurotoxic pattern as increase in frequency of miniature end-plate potentials (MEPPs) as well as in amplitude of end-plate potentials (EPPs); neuromuscular facilitation followed by complete and irreversible blockade without morphological evidence for muscle damage. In this work, we analysed the ultrastructural damage induced by Bothrops jararacussu and Bothrops bilineatus venoms and their PLA2 toxins (BthTX-I and Bbil-TX) in mouse isolated nerve-phrenic diaphragm preparations (PND)...
August 18, 2016: Microscopy Research and Technique
Mohammad Waseem, Heena Tabassum, Suhel Parvez
Neurotoxicity is a burdensome consequence of platinum-based chemotherapy that neutralizes the administration of effective dosage and often prompts treatment withdrawal. Oxaliplatin (Oxa), a third-era platinum analogue that is active against both early-organize and progressed colorectal growth, produces critical neurotoxicity. It has been reported that the Melatonin (Mel) is a pineal hormone its metabolites display important antioxidant properties in nervous system. There is dearth of literature involving the role of mitochondria and cytosolic compartments mediated Oxa-induced neurotoxicity and its underlying mechanisms are still debatable...
September 2016: Mitochondrion
U Anand, M Sinisi, M Fox, A MacQuillan, T Quick, Y Korchev, C Bountra, T McCarthy, P Anand
BACKGROUND: Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401...
2016: Molecular Pain
Yunxin Cai, Dandan Lu, Zhen Chen, Yi Ding, Nga N Chung, Tingyou Li, Peter W Schiller
Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities...
August 1, 2016: Bioorganic & Medicinal Chemistry Letters
Maximilian Weniger, Leonard Reinelt, Jens Neumann, Lesca Holdt, Matthias Ilmer, Bernhard Renz, Werner Hartwig, Jens Werner, Alexandr V Bazhin, Jan G D'Haese
Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications...
2016: Oxidative Medicine and Cellular Longevity
Xizhao Huang, Rongfang Deng, Weifeng Tu, Zurong Hu
BACKGROUND: Dexmedetomidine has been proposed as a novel anesthetic adjuvant. However, it remains unclear whether peripheral administration of dexmedetomidine is safe and effective to reduce acute postoperative pain. This study aimed to examine the effects of dexmedetomidine on neuropathic pain. METHODS: Adult male Sprague-Dawley rats were anaesthetized and randomly allocated into four groups (n = 8): Groups S, R, RD1, and RD5 were injected with saline, 0.5% ropivacaine, 0...
April 28, 2016: Asian Journal of Surgery
Olga Krupkova, Junichi Handa, Marian Hlavna, Juergen Klasen, Caroline Ospelt, Stephen John Ferguson, Karin Wuertz-Kozak
Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2 (total n = 36)...
2016: Oxidative Medicine and Cellular Longevity
Giovanna Traina
A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during beta-oxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies...
2016: Frontiers in Bioscience (Landmark Edition)
Anna-Karin Persson, Janneke G J Hoeijmakers, Mark Estacion, Joel A Black, Stephen G Waxman
Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy...
May 2016: Trends in Molecular Medicine
Eun Gyeong Lim, Guen Tae Kim, Se Hee Lee, Sang-Yong Kim, Young Min Kim
Colon cancer, a common malignancy, can occur due to poor eating habits and increasing age. Consequently, careful regulation of eating habits may serve as a possible method for preventing the occurrence or progression of colon cancer. Extracts of the fruit of Cnidium monnieri (L.) Cusson are well‑known as an effective herbal medicine for the treatment of pain in female genitalia and carbuncle. However, there have been no studies on the apoptotic effects of Cnidium monnieri (L.) Cusson (CME). Adenosine monophosphate‑activated protein kinase (AMPK), the major regulator of energy metabolism, is activated by metabolic stress, including hypoxia and glucose deprivation...
June 2016: Molecular Medicine Reports
Debkumar Pain, Andrew Dancis
Fe-S cluster assembly is an essential process for all cells. Impairment of Fe-S cluster assembly creates diseases in diverse and surprising ways. In one scenario, the loss of function of lipoic acid synthase, an enzyme with Fe-S cluster cofactor in mitochondria, impairs activity of various lipoamide-dependent enzymes with drastic consequences for metabolism. In a second scenario, the heme biosynthetic pathway in red cell precursors is specifically targeted, and iron homeostasis is perturbed, but lipoic acid synthesis is unaffected...
April 7, 2016: Current Opinion in Genetics & Development
Rajeshwary Ghosh, Soyun M Hwang, Ziyou Cui, Jennifer E Gilda, Aldrin V Gomes
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) like meclofenamate sodium (MS), used to reduce pain, has been associated with an increased risk of cardiovascular disease (CVD). Naproxen (NAP), another NSAID, is not associated with increased risk of CVD. The molecular mechanism(s) by which NSAIDs induce CVD is unknown. We investigated the effects of MS and NAP on protein homeostasis and cardiotoxicity in rat cardiac H9c2 cells and murine neonatal cardiomyocytes. MS, but not NAP, significantly inhibited proteasome activity and reduced cardiac cell viability at pharmacological levels found in humans...
May 2016: Journal of Molecular and Cellular Cardiology
Hasan Balaban, Mustafa Nazıroğlu, Kadir Demirci, İshak Suat Övey
Inhibition of Ca(2+) entry into the hippocampus and dorsal root ganglion (DRG) through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is the current standard of care in neuronal diseases such as Alzheimer's disease, dementia, and peripheral pain. Oxidative stress activates Ca(2+)-permeable TRPM2 and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and TRPV1 channel antagonist in the hippocampus and DRG. In this study, we investigated the neuroprotective properties of Se in primary hippocampal and DRG neuron cultures of aged rats when given alone or in combination with scopolamine (SCOP)...
March 28, 2016: Molecular Neurobiology
Simon C Baker, Saqib Shabir, Nikolaos T Georgopoulos, Jennifer Southgate
Recreational abuse of ketamine has been associated with the emergence of a new bladder pain syndrome, ketamine-induced cystitis, characterized by chronic inflammation and urothelial ulceration. We investigated the direct effects of ketamine on normal human urothelium maintained in organ culture or as finite cell lines in vitro. Exposure of urothelium to ketamine resulted in apoptosis, with cytochrome c release from mitochondria and significant subsequent caspase 9 and 3/7 activation. The anesthetic mode-of-action for ketamine is mediated primarily through N-methyl d-aspartate receptor (NMDAR) antagonism; however, normal (nonimmortalized) human urothelial cells were unresponsive to NMDAR agonists or antagonists, and no expression of NMDAR transcript was detected...
May 2016: American Journal of Pathology
Gabriel Alejandro Bonaterra, Hanna Then, Lisa Oezel, Hans Schwarzbach, Matthias Ocker, Kati Thieme, Pietro Di Fazio, Ralf Kinscherf
BACKGROUND: Fibromyalgia (FM) is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS), we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice...
2016: PloS One
Mehmet Cemal Kahya, Mustafa Nazıroğlu, İshak Suat Övey
Neuropathic pain and hippocampal injury can arise from the overload of diabetes-induced calcium ion (Ca(2+)) entry and oxidative stress. The transient receptor potential (TRP) melastatin 2 (TRPM2) and TRP vanilloid type 1 (TRPV1) are expressed in sensory neurons and hippocampus. Moreover, activations of TRPM2 and TRPV1 during oxidative stress have been linked to neuronal death. Melatonin (MEL) and selenium (Se) have been considered potent antioxidants that detoxify a variety of reactive oxygen species (ROS) in neurological diseases...
March 9, 2016: Molecular Neurobiology
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