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https://www.readbyqxmd.com/read/28814984/protective-mechanisms-of-the-mitochondrial-derived-peptide-humanin-in-oxidative-and-endoplasmic-reticulum-stress-in-rpe-cells
#1
REVIEW
Leonid Minasyan, Parameswaran G Sreekumar, David R Hinton, Ram Kannan
Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss and is characterized by progressive degeneration of the retina resulting in loss of central vision. The retinal pigment epithelium (RPE) is a critical site of pathology of AMD. Mitochondria and the endoplasmic reticulum which lie in close anatomic proximity to each other are targets of oxidative stress and endoplasmic reticulum (ER) stress, respectively, and contribute to the progression of AMD. The two organelles exhibit close interactive function via various signaling mechanisms...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28802666/humanin-directly-protects-cardiac-mitochondria-against-dysfunction-initiated-by-oxidative-stress-by-decreasing-complex-i-activity
#2
Savitree Thummasorn, Krekwit Shinlapawittayatorn, Juthamas Khamseekaew, Thidarat Jaiwongkam, Siriporn C Chattipakorn, Nipon Chattipakorn
Humanin (HN) is an endogenous peptide that exerts cytoprotection against oxidative stress and apoptosis. We recently reported that Humanin analogue (HNG) pretreatment can reduce reactive oxygen species production in the heart subjected to ischemia/reperfusion (I/R) injury via attenuating mitochondrial dysfunction. However, it is unclear if HNG has direct effects on mitochondrial function against oxidative stress. Thus, we sought to determine the effects of HNG on mitochondrial function under hydrogen peroxide (H2O2) induced oxidative stress in isolated cardiac mitochondria...
August 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28798389/the-mitochondrial-derived-peptides-humanins14g-and-small-humanin-like-peptide-2-exhibit-chaperone-like-activity
#3
Alan K Okada, Kazuki Teranishi, Fleur Lobo, J Mario Isas, Jialin Xiao, Kelvin Yen, Pinchas Cohen, Ralf Langen
Mitochondrial-derived peptides (MDPs) and their analogs have emerged as wide-spectrum, stress response factors protective in amyloid disease models. MDP cytoprotective functions are generally attributed to anti-apoptotic activity, however, little is known about their capacity to facilitate the cell's unfolded protein response via direct interactions with amyloidogenic proteins. Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28731445/colivelin-ameliorates-impairments-in-cognitive-behaviors-and-synaptic-plasticity-in-app-ps1-transgenic-mice
#4
Meina Wu, Hui Shi, Yexin He, Li Yuan, Xuesong Qu, Jun Zhang, Zhaojun Wang, Hongyan Cai, Jinshun Qi
Alzheimer's disease (AD) is the most common cause of dementia, and effective therapeutics are lacking. Colivelin (CLN), a novel, strong humanin derivative, is effective in vitro in preventing cell death induced by AD-causative genes and amyloid-β protein (Aβ) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents Aβ25-35-induced deficits in spatial memory and synaptic plasticity in normal rats. Here, we further observed the effects of chronically intranasally (i...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28726777/humanin-g-hng-protects-age-related-macular-degeneration-amd-transmitochondrial-arpe-19-cybrids-from-mitochondrial-and-cellular-damage
#5
Sonali Nashine, Pinchas Cohen, Marilyn Chwa, Stephanie Lu, Anthony B Nesburn, Baruch D Kuppermann, M Cristina Kenney
Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726291/high-dose-humanin-analogue-applied-during-ischemia-exerts-cardioprotection-against-ischemia-reperfusion-injury-by-reducing-mitochondrial-dysfunction
#6
Savitree Thummasorn, Krekwit Shinlapawittayatorn, Siriporn C Chattipakorn, Nipon Chattipakorn
Although the gold standard treatment for acute myocardial infarction is reperfusion therapy, reperfusion itself can cause myocardial damage via induction of cardiac mitochondrial dysfunction. This can lead to increased myocardial infarct size, arrhythmias and left ventricular (LV) dysfunction. Recently, a newly discovered peptide, Humanin, has been shown to exert several beneficial effects including anti-oxidative and anti-apoptosis effects. We recently reported that a Humanin analogue (HNG, 84 μg/kg) given prior to cardiac ischemia exerted cardioprotection against I/R injury, but failed to do so when it was given after ischemia was induced...
July 20, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28720038/neuroprotective-effect-of-g-14-humanin-on-global-cerebral-ischemia-reperfusion-by-activation-of-socs3-stat3-mcl-1-signal-transduction-pathway-in-rats
#7
Guangsheng Gao, Huaihai Fan, Xiaoying Zhang, Fusen Zhang, Haiyan Wu, Feng Qi, Lei Zhao, Yun Li
OBJECTIVE: Humanin (HN) has been identified to suppress neuron death. Gly(14)-HN (HNG), as a variant of HN, can decrease infarct volume after ischemia/reperfusion (I/R) injury. This study aimed to investigate the neuroprotective mechanism of HNG on global cerebral I/R (GI) in rats. METHODS: Rats were randomly divided into 13 groups: Sham group, GI groups and HNG groups. Both GI group and HNG groups included six time points (1, 3, 6, 12, 24, and 72 h). At 24 h after reperfusion, Nissl staining was used to observe positive neurons, and p-STAT3, MCL-1, SOCS3, Bax and Caspase-3 in different groups were detected by immunohistochemistry...
July 18, 2017: Neurological Research
https://www.readbyqxmd.com/read/28592211/calmodulin-like-skin-protein-is-downregulated-in-human-cerebrospinal-fluids-of-alzheimer-s-disease-patients-with-apolipoprotein-e4-a-pilot-study-using-postmortem-samples
#8
Yuichi Hashimoto, Takahiko Umahara, Haruo Hanyu, Toshihiko Iwamoto, Masaaki Matsuoka
OBJECTIVE: Calmodulin-like skin protein (CLSP) is a secreted peptide that inhibits neuronal cell death, linked to Alzheimer's disease (AD), by binding to the heterotrimeric humanin receptor and activating an intracellular survival pathway. CLSP is only expressed in skin keratinocytes and related epithelial cells, circulates in the blood stream, and passes the blood-cerebrospinal fluid (CSF) barrier. In the current study, we addressed the issues as to whether CLSP functions in the central nervous system and whether the concentration of CLSP is reduced in the CSFs of AD patients...
June 7, 2017: Neurological Research
https://www.readbyqxmd.com/read/28574175/mitochondrial-derived-peptides-as-novel-regulators-of-metabolism
#9
Su-Jeong Kim, Jialin Xiao, Junxiang Wan, Pinchas Cohen, Kelvin Yen
Mitochondrial derived peptides represent a new class of circulating signalling molecules. Humanin, the first member of this class, has been shown to have several metabolic effects such as reducing weight gain and visceral fat and increasing glucose stimulated insulin release. The discovery of several other new members such as MOTS-c and SHLP1-6, have further added to this group. These new peptides have also been found to affect metabolism with MOTS-c potently decreasing weight gain in mice on a high fat diet...
June 2, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28462847/breaking-the-ritual-metabolic-cycle-in-order-to-save-acetyl-coa-a-potential-role-for-mitochondrial-humanin-in-t2-bladder-cancer-aggressiveness
#10
Nesreen Nabil Omar, Reham Fathy Tash, Youssef Shoukry, Karim Omar ElSaeed
INTRODUCTION: Cancer cells may exhibit outsourcing of their high energy need in order to avoid the intrinsic mitochondrial apoptosis. Reduced mitochondrial respiration and accumulation of mitochondrial genome mutations are among metabolic transformations in this regard. Mitochondrial humanin (MT-RNR2) is a small peptide with anti-apoptotic activities attributed to binding some pro-apoptotic proteins. AIM OF THE WORK: The current study aims at investigating the expression of mitochondrial humanin in bladder tumor cells and the possible casting of humanin anti-apoptotic action through orchestrating some of the mitochondrial metabolic enzymes...
April 24, 2017: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/28458518/humanin-rescues-cultured-rat-cortical-neurons-from-nmda-induced-toxicity-through-the-alleviation-of-mitochondrial-dysfunction
#11
Ai-Ling Cui, Ying-Hua Zhang, Jian-Zhong Li, Tianbin Song, Xue-Min Liu, Hui Wang, Ce Zhang, Guo-Lin Ma, Hui Zhang, Kefeng Li
N-methyl-D-aspartate (NDMA) receptor-mediated excitotoxicity has been implicated in a variety of pathological situations such as Alzheimer's disease (AD) and Parkinson's disease. However, no effective treatments for the same have been developed so far. Humanin (HN) is a 24-amino acid peptide originally cloned from the brain of patients with AD and it prevents stress-induced cell death in many cells/tissues. In our previous study, HN was found to effectively rescue rat cortical neurons. It is still not clear whether HN protects the neurons through the attenuation of mitochondrial dysfunction...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28378125/humanin-inhibits-apoptosis-in-pituitary-tumor-cells-through-several-signaling-pathways-including-nf-%C3%AE%C2%BAb-activation
#12
María Florencia Gottardo, Mariela Moreno Ayala, Jimena Ferraris, Sandra Zárate, Daniel Pisera, Marianela Candolfi, Gabriela Jaita, Adriana Seilicovich
Humanin (HN) and Rattin (HNr), its homologous in the rat, are peptides with cytoprotective action in several cell types such as neurons, lymphocytes and testicular germ cells. Previously, we have shown that HNr is expressed in pituitary cells and that HN inhibited the apoptotic effect of TNF-α in both normal and tumor pituitary cells. The aim of the present study was to identify signaling pathways that mediate the antiapoptotic effect of HN in anterior pituitary cells from ovariectomized rats and in GH3 cells, a somatolactotrope cell line...
April 4, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28361841/effects-of-humanin-on-experimental-colitis-induced-by-2-4-6-trinitrobenzene-sulphonic-acid-in-rats
#13
Fatma A Gultekin, Ali U Emre, Sevim K Celik, Figen Barut, Ufuk Tali, Demet Sumer, Ummuhani O Turkcu
BACKGROUND/AIM: The excessive apoptosis of intestinal epithelial cells (IECs) partly accounts for the development of colonic inflammation and eventually results in ulcerative colitis (UC). Humanin, an endogenous anti-apoptotic peptide, has previously been shown to protect against Alzheimer's disease and a variety of cellular insults. The present study aimed to investigate the effects of glysin variant of humanin (HNG) on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats...
March 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28282805/humanin-specifically-interacts-with-amyloid-%C3%AE-oligomers-and-counteracts-their-in-vivo-toxicity
#14
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
https://www.readbyqxmd.com/read/28250736/endoplasmic-reticulum-mitochondrial-crosstalk-a-novel-role-for-the-mitochondrial-peptide-humanin
#15
REVIEW
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
https://www.readbyqxmd.com/read/28110609/serum-humanin-concentrations-in-women-with-pre-eclampsia-compared-to-women-with-uncomplicated-pregnancies
#16
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
https://www.readbyqxmd.com/read/27923980/humanin-skeletal-muscle-protein-levels-increase-after-resistance-training-in-men-with-impaired-glucose-metabolism
#17
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
https://www.readbyqxmd.com/read/27815075/gly-14-humanin-inhibits-ox-ldl-uptake-and-stimulates-cholesterol-efflux-in-macrophage-derived-foam-cells
#18
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
https://www.readbyqxmd.com/read/27814910/humanin-ameliorates-diazepam-induced-memory-deficit-in-mice
#19
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...
April 2017: Neuropeptides
https://www.readbyqxmd.com/read/27783653/humanin-protects-rpe-cells-from-endoplasmic-reticulum-stress-induced-apoptosis-by-upregulation-of-mitochondrial-glutathione
#20
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
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