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https://www.readbyqxmd.com/read/29212276/low-circulating-levels-of-the-mitochondrial-peptide-hormone-shlp2-novel-biomarker-for-prostate-cancer-risk
#1
Jialin Xiao, Lauren Howard, Junxiang Wan, Emily Wiggins, Adriana Vidal, Pinchas Cohen, Stephen J Freedland
Context: Mitochondrial DNA mutations and dysfunction are associated with prostate cancer (PCa). Small humanin-like peptide-2 (SHLP2) is a novel mitochondrial-encoded peptide and an important mitochondrial retrograde signaling molecule. Objective: To determine whether serum SHLP2 concentration is associated with PCa risk and whether associations are race-specific.Design, Setting and Participants: Patients undergoing prostate biopsy were recruited from the Durham Veterans Affairs hospital...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187525/humanin-is-an-endogenous-activator-of-chaperone-mediated-autophagy
#2
Zhenwei Gong, Inmaculada Tasset, Antonio Diaz, Jaime Anguiano, Emir Tas, Lingguang Cui, Regina Kuliawat, Honghai Liu, Bernhard Kühn, Ana Maria Cuervo, Radhika Muzumdar
Chaperone-mediated autophagy (CMA) serves as quality control during stress conditions through selective degradation of cytosolic proteins in lysosomes. Humanin (HN) is a mitochondria-associated peptide that offers cytoprotective, cardioprotective, and neuroprotective effects in vivo and in vitro. In this study, we demonstrate that HN directly activates CMA by increasing substrate binding and translocation into lysosomes. The potent HN analogue HNG protects from stressor-induced cell death in fibroblasts, cardiomyoblasts, neuronal cells, and primary cardiomyocytes...
November 29, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29164613/calmodulin-like-skin-protein-protects-against-spatial-learning-impairment-in-a-mouse-model-of-alzheimer-disease
#3
Shinya Kusakari, Mikiro Nawa, Katsuko Sudo, Masaaki Matsuoka
Humanin and calmodulin-like skin protein (CLSP) inhibits Alzheimer disease (AD)-related neuronal cell death via the heterotrimeric humanin receptor in vitro. It has been suggested that CLSP is a central agonist of the heterotrimeric humanin receptor in vivo. To investigate the role of CLSP in the AD pathogenesis in vivo, we generated mouse CLSP-1 transgenic mice, crossed them with the APPswe/PSEN1dE9 mice, a model mouse of AD, and examined the effect of CLSP overexpression on the pathological phenotype of the AD mouse model...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29161500/a-small-molecule-mimetic-of-the-humanin-peptide-as-a-candidate-for-modulating-nmda-induced-neurotoxicity
#4
Mohammad Parvez Alam, Tina Bilousova, Patricia Spilman, Kanagasabai Vadivel, Dongsheng Bai, Denis Evseenko, Varghese John
Humanin (HN), a 24-amino acid bioactive peptide, has been shown to increase cell survival of neurons after exposure to Aβ and NMDA-induced toxicity and thus could be beneficial in the treatment of Alzheimer's disease (AD). The neuroprotection by HN is reported to be primarily through its agonist binding properties to the gp130 receptor. However, peptidic nature of HN presents challenges in its development as a therapeutic for AD. We report here for the first time the elucidation of the binding site of Humanin (HN) peptide to gp130 receptor extracellular domain through modeling and the synthesis of small molecule mimetics that interact with the HN binding site on the gp130 receptor that provides protection against NMDA-induced neurotoxicity in primary hippocampal neurons...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29070438/humanin-affects-object-recognition-and-gliosis-in-short-term-cuprizone-treated-mice
#5
Minetaka Murakami, Masatoshi Nagahama, Yoichiro Abe, Takako Niikura
Humanin (HN) is a 24-residue peptide that manipulates cell survival under various stresses. A highly potent HN derivative, HNG, reduced amyloid burden and neuroinflammation and suppressed cognitive impairment in Alzheimer's disease model mice. Cuprizone (CPZ), a copper chelator, provokes demyelination in the central nervous system of mice. A shorter (one week) exposure to CPZ induces schizophrenia-like behavior and glial activation prior to demyelination. We tested the effect of HNG on these short-term responses to CZP in mice...
October 14, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29058763/s14g-humanin-alleviates-insulin-resistance-and-increases-autophagy-in-neurons-of-app-ps1-transgenic-mouse
#6
Kun Han, Ning Jia, Yi Zhong, Xiuli Shang
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by Aβ plaque deposition in the brain, which is related to the disorder of autophagosome maturation, transport and formation of autolysosome. Notably, abnormal insulin signaling is connected with cognitive dysfunction in AD. In this study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism by which S14G-humanin (HNG) improved autophagy and insulin signaling in AD brain. Immunohistochemistry was used to determine the levels of mTOR and Aβ deposition, and Western blot analysis was used to determine IRS-1, IRS-1 pSEr636, ULK1, p62, LC3 I/LC3 II protein levels...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29043002/humanin-analogue-s14g-humanin-has-neuroprotective-effects-against-oxygen-glucose-deprivation-reoxygenation-by-reactivating-jak2-stat3-signaling-through-the-pi3k-akt-pathway
#7
Guang-Sheng Gao, Yun Li, Heng Zhai, Jing-Wen Bi, Fu-Sen Zhang, Xiao-Ying Zhang, Shao-Hua Fan
Stroke, characterized by a disruption of blood supply to the brain, is a major cause of morbidity and mortality worldwide. Although humanin, a 24-amino acid polypeptide, has been identified to have multiple neuroprotective functions, the level of humanin in plasma has been demonstrated to decrease with age, which likely limits the effects against stroke injury. A potent humanin analogue, S14G-humanin (HNG), generated by replacement of Ser14 with glycine, has been demonstrated to have 1,000-fold stronger biological activity than humanin...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28994791/subcellular-fractionation-for-erk-activation-upon-mitochondrial-derived-peptide-treatment
#8
Su-Jeong Kim, Jialin Xiao, Pinchas Cohen, Kelvin Yen
Mitochondrial-derived peptides (MDPs) are a new class of peptides that are encoded by small open reading frames within other known genes of the mitochondrial genome. MDPs have a wide variety of biological effects such as protecting neurons from apoptosis, improving metabolic markers, and protecting cells from chemotherapy. Humanin was the first MDP to be discovered and is the most studied peptide among the MDP family. The membrane receptors and downstream signaling pathways of humanin have been carefully characterized...
September 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28814984/protective-mechanisms-of-the-mitochondrial-derived-peptide-humanin-in-oxidative-and-endoplasmic-reticulum-stress-in-rpe-cells
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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/mitochondrially-derived-peptides-as-novel-regulators-of-metabolism
#17
Su-Jeong Kim, Jialin Xiao, Junxiang Wan, Pinchas Cohen, Kelvin Yen
Mitochondrially 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, has 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...
November 1, 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
#18
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
#19
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
#20
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
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