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Margherita Romeo, Matteo Stravalaci, Marten Beeg, Alessandro Rossi, Fabio Fiordaliso, Alessandro Corbelli, Mario Salmona, Marco Gobbi, Alfredo Cagnotto, Luisa Diomede
The 24-residue peptide humanin (HN) has been proposed as peptide-based inhibitors able to interact directly with amyloid-β (Aβ) oligomers and interfere with the formation and/or biological properties of toxic Aβ species. When administered exogenously HN, or its synthetic S14G-derivative (HNG), exerted multiple cytoprotective effects, counteracting the Aβ-induced toxicity. Whether these peptides interact directly with Aβ, particularly with the soluble oligomeric assemblies, remains largely unknown. We here investigated the ability of HN and HNG to interact directly with highly aggregating Aβ42, and interfere with the formation and toxicity of its oligomers...
March 6, 2017: Journal of Alzheimer's Disease: JAD
Parameswaran G Sreekumar, David R Hinton, Ram Kannan
In this review, the interactive mechanisms of mitochondria with the endoplasmic reticulum (ER) are discussed with emphasis on the potential protective role of the mitochondria derived peptide humanin (HN) in ER stress. The ER and mitochondria are dynamic organelles capable of modifying their structure and function in response to changing environmental conditions. The ER and mitochondria join together at multiple sites and form mitochondria-ER associated membranes that participate in signal transduction pathways that are under active investigation...
January 2017: Neural Regeneration Research
Panagiotis Nikolakopoulos, Georgios Tzimagiorgis, Dimitrios G Goulis, Fani Chatzopoulou, Leonidas Zepiridis, Dimitrios Vavilis
PURPOSE: To compare serum humanin concentrations in pregnant women with and without pre-eclampsia (PE). MATERIALS AND METHODS: A case-control study where pregnant women (PE group, n = 37; control group, n = 34) studied through history parameters (gynecological, obstetrical, personal, and family), physical and sonographic examination parameters [body mass index (BMI), blood pressure obstetrical ultrasound], and biochemical/hormonal assays [creatinine, urea, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), uric acid, platelets, urinary protein, and humanin]...
February 9, 2017: Journal of Maternal-fetal & Neonatal Medicine
Eva-Karin Gidlund, Ferdinand von Walden, Mika Venojärvi, Ulf Risérus, Olli J Heinonen, Jessica Norrbom, Carl Johan Sundberg
Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Whether skeletal muscle HN gene or protein expression is influenced by exercise remains unknown. In this intervention study we show, for the first time, that HN protein levels increase in human skeletal muscle following 12 weeks of resistance training in persons with prediabetes. Male subjects (n = 55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training, Nordic walking or a control group...
December 2016: Physiological Reports
Wa-Wa Zhu, Shu-Rong Wang, Zhi-Hua Liu, Yong-Jun Cao, Fen Wang, Jing Wang, Chun-Feng Liu, Ying Xie, Ying Xie, Yan-Lin Zhang
Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264...
January 1, 2017: Biochemical and Biophysical Research Communications
Minetaka Murakami, Masatoshi Nagahama, Takuma Maruyama, Takako Niikura
Humanin (HN) is an endogenous 24-residue peptide. A highly potent HN derivative, S14G-HN, which has a substitution of serine 14 to glycine, reduced amyloid burden and suppressed cognitive impairment in a mouse model of Alzheimer's disease. S14G-HN also suppressed amnesia induced by a muscarinic receptor antagonist in rodents. To understand the effects of HN on brain function, we tested the effect of S14G-HN on diazepam (DZP)-induced memory impairment and anxiety in mice using the object recognition test and zero-maze test, respectively...
October 29, 2016: Neuropeptides
Douglas Matsunaga, Parameswaran G Sreekumar, Keijiro Ishikawa, Hiroto Terasaki, Ernesto Barron, Pinchas Cohen, Ram Kannan, David R Hinton
Humanin (HN) is a small mitochondrial-encoded peptide with neuroprotective properties. We have recently shown protection of retinal pigmented epithelium (RPE) cells by HN in oxidative stress; however, the effect of HN on endoplasmic reticulum (ER) stress has not been evaluated in any cell type. Our aim here was to study the effect of HN on ER stress-induced apoptosis in RPE cells with a specific focus on ER-mitochondrial cross-talk. Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL)...
2016: PloS One
S P Pantazatos, Y-Y Huang, G B Rosoklija, A J Dwork, V Arango, J J Mann
Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem...
August 16, 2016: Molecular Psychiatry
Hui Zhao, Soushi Sonada, Akihiro Yoshikawa, Kousaku Ohinata, Masaaki Yoshikawa
Rubimetide (Met-Arg-Trp), which had been isolated as an antihypertensive peptide from an enzymatic digest of spinach ribulose-bisphosphate carboxylase/oxygenase (Rubisco), showed anxiolytic-like activity prostaglandin (PG) D2-dependent manner in the elevated plus-maze test after administration at a dose of 0.1mg/kg (ip.) or 1mg/kg (p.o.) in male mice of ddY strain. In this study, we found that rubimetide has weak affinities for the FPR1 and FPR2, subtypes of formyl peptide receptor (FPR). The anxiolytic-like activity of rubimetide (0...
September 2016: Peptides
Savitree Thummasorn, Nattayaporn Apaijai, Sasiwan Kerdphoo, Krekwit Shinlapawittayatorn, Siriporn C Chattipakorn, Nipon Chattipakorn
AIM: Myocardial reperfusion via the re-canalization of occluded coronary arteries is gold standard for the treatment of acute myocardial infarction. However, reperfusion itself can cause myocardial damage due to increased reactive oxygen species (ROS) production, a process known as ischemia/reperfusion (I/R) injury. Cardiac mitochondria are the major organelle of ROS production in the heart. Cardiac mitochondrial dysfunction caused by an increased ROS production can increase cardiac arrhythmia incidence, myocardial infarct size, and cardiac dysfunction...
December 2016: Cardiovascular Therapeutics
Su-Jeong Kim, Noel Guerrero, Gabriella Wassef, Jialin Xiao, Hemal H Mehta, Pinchas Cohen, Kelvin Yen
Humanin is a small secreted peptide that is encoded in the mitochondrial genome. Humanin and its analogues have a protective role in multiple age-related diseases including type 2 diabetes and Alzheimer's disease, through cytoprotective and neuroprotective effects both in vitro and in vivo. However, the humanin-mediated signaling pathways are not well understood. In this paper, we demonstrate that humanin acts through the GP130/IL6ST receptor complex to activate AKT, ERK1/2, and STAT3 signaling pathways. Humanin treatment increases phosphorylation in AKT, ERK 1/2, and STAT3 where PI3K, MEK, and JAK are involved in the activation of those three signaling pathways, respectively...
July 26, 2016: Oncotarget
Nesreen Alsanousi, Toshihiko Sugiki, Kyoko Furuita, Masatomo So, Young-Ho Lee, Toshimichi Fujiwara, Chojiro Kojima
Humanin comprising 24 amino acid residues is a bioactive peptide that has been isolated from the brain tissue of patients with Alzheimer's disease. Humanin reportedly suppressed aging-related death of various cells due to amyloid fibrils and oxidative stress. There are reports that the cytoprotective activity of Humanin was remarkably enhanced by optical isomerization of the Ser14 residue from l to d form, but details of the molecular mechanism remained unclear. Here we demonstrated that Humanin d-Ser14 exhibited potent inhibitory activity against fibrillation of amyloid-β and remarkably higher binding affinity for amyloid-β than that of the Humanin wild-type and S14G mutant...
September 2, 2016: Biochemical and Biophysical Research Communications
Li Yuan, Xiao-Jie Liu, Wei-Na Han, Qing-Shan Li, Zhao-Jun Wang, Mei-Na Wu, Wei Yang, Jin-Shun Qi
Alzheimer disease (AD), a progressive neurodegenerative disorder, is characterized by cognitive decline and the accumulation of senile plaques in the brain. Amyloid β protein (Aβ) in the plaques is thought to be responsible for the memory loss in AD patients. [Gly14]-humanin (HNG), a derivative of humanin (HN), has much stronger neuroprotective effects than natural HN in vitro. However, clarification of the Aβ active center and the neuroprotective mechanism of HN still need in vivo evidence. The present study first compared the in vivo biological effects of three Aβ fragments (1-42, 31-35, and 35-31) on spatial memory in rats, and investigated the neuroprotective effects and molecular mechanisms of HNG...
August 2016: Neuroscience Bulletin
Changhan Lee, Kyung Hwa Kim, Pinchas Cohen
Mitochondria are ancient organelles that are thought to have emerged from once free-living α-proto-bacteria. As such, they still possess several bacterial-like qualities, including a semi-autonomous genetic system, complete with an independent genome and a unique genetic code. The bacterial-like circular mitochondrial DNA (mtDNA) has been described to encode 37 genes, including 22 tRNAs, 2 rRNAs, and 13 mRNAs. Two additional peptides reported to originate from the mtDNA, namely humanin (Hashimoto et al., 2001; Ikone et al...
November 2016: Free Radical Biology & Medicine
Annet Voigt, Herbert F Jelinek
Mitochondrial RNR-2 (mt-RNR2, humanin) has been shown to play a role in protecting several types of cells and tissues from the effects of oxidative stress. Humanin (HN) functions through extracellular and intracellular pathways adjusting mitochondrial oxidative phosphorylation and ATP production. Addition of HN improved insulin sensitivity in animal models of diabetes mellitus but no clinical studies have been carried out to measure HN levels in humans associated with hyperglycemia. The plasma levels of HN in participants attending a diabetes complications screening clinic were measured...
May 2016: Physiological Reports
J Xiao, S-J Kim, P Cohen, K Yen
Humanin is the first newly discovered peptide encoded in the mitochondrial genome in over three decades. It is the first member of a novel class of mitochondrial derived peptides. This small, 24 amino acid peptide was initially discovered to have neuroprotective effects and subsequent experiments have shown that it is beneficial in a diverse number of disease models including stroke, cardiovascular disease, and cancer. Over a decade ago, our lab found that humanin bound IGFBP-3 and more recent studies have found it to decrease circulating IGF-I levels...
August 2016: Growth Hormone & IGF Research
Laura J Cobb, Changhan Lee, Jialin Xiao, Kelvin Yen, Richard G Wong, Hiromi K Nakamura, Hemal H Mehta, Qinglei Gao, Carmel Ashur, Derek M Huffman, Junxiang Wan, Radhika Muzumdar, Nir Barzilai, Pinchas Cohen
Mitochondria are key players in aging and in the pathogenesis of age-related diseases. Recent mitochondrial transcriptome analyses revealed the existence of multiple small mRNAs transcribed from mitochondrial DNA (mtDNA). Humanin (HN), a peptide encoded in the mtDNA 16S ribosomal RNA region, is a neuroprotective factor. An in silico search revealed six additional peptides in the same region of mtDNA as humanin; we named these peptides small humanin-like peptides (SHLPs). We identified the functional roles for these peptides and the potential mechanisms of action...
April 2016: Aging
Sirinart Kumfu, Savitree T Charununtakorn, Thidarat Jaiwongkam, Nipon Chattipakorn, Siriporn C Chattipakorn
What is the central question of this study? Myocardial ischaemia-reperfusion (I/R) injury causes interference in the systemic circulation and damages not only the heart but also several vital organs, including the brain. Recently, a novel peptide called humanin has been shown to exert potent neuroprotective effects. However, the effect of humanin on the brain during cardiac I/R injury has not yet been investigated. What is the main finding and its importance? The I/R injury caused blood-brain barrier breakdown, increased brain oxidative stress and resulted in mitochondrial dysfunction...
June 1, 2016: Experimental Physiology
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