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https://www.readbyqxmd.com/read/29432738/humanin-promotes-mitochondrial-biogenesis-in-pancreatic-min6-%C3%AE-cells
#1
Qingqing Qin, Jieqiong Jin, Fang He, Yongqin Zheng, Tingting Li, Yun Zhang, Jundong He
Mitochondrial dysfunction is associated with β-cell failure and insulin resistance in diabetes. Humanin is an endogenous cytoprotective peptide. In the current study, we aimed to define the effects of Humanin on mitochondrial biogenesis in pancreatic β-cells. Our findings demonstrated that Humanin treatment significantly increased the expression of PGC-1α and its downstream target genes NRF1 and TFAM in MIN6 β-cells. Notably, Humanin treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial mass, elevating mtDNA/nDNA ratio, and stimulating the expression of cytochrome B, which were suppressed by the specific AMPK inhibitor compound C...
February 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29386715/aeromedical-solutions-for-aerospace-safety
#2
Pawan Kapoor, Deepak Gaur
All facets of activity in the speciality of Aviation Medicine are essentially aimed at enhancing aerospace safety. This paper highlights some innovative changes brought about by Aerospace Medicine in the three major fields of the speciality namely, medical evaluation, aeromedical training and research. Based on lab and field studies, military aircrew are now permitted flying with Modifinil as 'Go' Pill and Zolpidem as 'No-Go' Pill during sustained operations. Several other drugs for disabilities like Hypertension and CAD are now permitted for aviators...
October 2017: Medical Journal, Armed Forces India
https://www.readbyqxmd.com/read/29376862/humanin-exerts-neuroprotection-during-cardiac-ischemia-reperfusion-injury
#3
Sirinart Kumfu, Savitree T Charununtakorn, Thidarat Jaiwongkam, Nipon Chattipakorn, Siriporn C Chattipakorn
 Cardiac ischemia-reperfusion (I/R) injury has been shown to impair brain function. Humanin analogue (HNG) given prior to cardiac ischemia has been shown to attenuate both heart and brain mitochondrial dysfunction caused by cardiac I/R injury. In a clinical setting, patients received medical treatment for acute myocardial infarction either during or after the onset of myocardial ischemia; thus, in this study, we tested the hypothesis that the administration of HNG during cardiac I/R injury has therapeutic potential for brain protection...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29352443/baculovirus-based-gene-silencing-of-humanin-for-the-treatment-of-pituitary-tumors
#4
María Florencia Gottardo, Matías L Pidre, Camila Zuccato, Antonela S Asad, Mercedes Imsen, Gabriela Jaita, Marianela Candolfi, Víctor Romanowski, Adriana Seilicovich
Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells...
January 19, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29212276/low-circulating-levels-of-the-mitochondrial-peptide-hormone-shlp2-novel-biomarker-for-prostate-cancer-risk
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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