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Autophagy

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Full-Text Articles in Life Sciences

Glutaminase - A Potential Target For Cancer Treatment, Josephine Anthony, Sureka Varalakshmi, Ashok Kumar Sekar, Nalini Devarajan, Balamurugan Janakiraman, Rajendran Peramaiyan May 2024

Glutaminase - A Potential Target For Cancer Treatment, Josephine Anthony, Sureka Varalakshmi, Ashok Kumar Sekar, Nalini Devarajan, Balamurugan Janakiraman, Rajendran Peramaiyan

BioMedicine

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions. Glutaminolysis linked with autophagy, which is mediated via mTORC1, also serves as a promising target for cancer therapy. Glutamine also plays a vital role in maintaining redox homeostasis. Inhibition of …


The Common Wall Lizard Podarcis Muralis (Reptilia: Lacertidae) Shows Diverse Food Preferences And Intraspecific Difference: A Study Case From Bulgaria, Emiliya Vacheva, Borislav Naumov May 2024

The Common Wall Lizard Podarcis Muralis (Reptilia: Lacertidae) Shows Diverse Food Preferences And Intraspecific Difference: A Study Case From Bulgaria, Emiliya Vacheva, Borislav Naumov

Turkish Journal of Zoology

The Common wall lizard (Podarcis muralis) has the largest range among the genus Podarcis. Although there are a number of studies on its diet, data on regional level remains insufficient, particularly from a purely ecological perspective. We investigated 194 individual faecal samples of P. muralis obtained from two localities in western Bulgaria with the aim of clarifying the composition of the trophic spectrum of the species, as well as the intra-population characteristics in terms of age and sex. In one study site we compared the realized trophic niche (prey items from the faecal pellets) with the fundamental (invertebrates collected via …


Simvastatin Induces Autophaghy-Mediated Cell Death In Metastatic Breast Cancer Cells, Jessica Allagoa May 2024

Simvastatin Induces Autophaghy-Mediated Cell Death In Metastatic Breast Cancer Cells, Jessica Allagoa

Theses (2016-Present)

Breast cancer remains one of the leading causes of cancer deaths among women. Due to the limited effectiveness of current anticancer drugs, ongoing research has extended towards alternative drug categories for potential treatments. Recent findings indicate that statins possess the ability to suppress tumors across various cell types. Traditionally, statins are known as a class of cholesterol-lowering agents and function by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, a key enzyme in the mevalonate pathway. However, statins can also suppress cell proliferation and ultimately lead to cell death, which includes Type I apoptosis-induced cell death or Type II autophagy-induced cell death. Autophagy is …


Momkk1 And Moatg1 Dichotomously Regulating Autophagy And Pathogenicity Through Moatg9 Phosphorylation In Magnaporthe Oryzae, Yun Kong, Pusheng Guo, Jiayun Xu, Jiaxu Li, Miao Wu, Ziqi Zhang, Yifan Wang, Xinyu Liu, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang Mar 2024

Momkk1 And Moatg1 Dichotomously Regulating Autophagy And Pathogenicity Through Moatg9 Phosphorylation In Magnaporthe Oryzae, Yun Kong, Pusheng Guo, Jiayun Xu, Jiaxu Li, Miao Wu, Ziqi Zhang, Yifan Wang, Xinyu Liu, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy is a central biodegradation pathway critical in eliminating intracellular cargo to maintain cellular homeostasis and improve stress resistance. At the same time, the key component of the mitogen-activated protein kinase cascade regulating cell wall integrity signaling MoMkk1 has an essential role in the autophagy of the rice blast fungus Magnaporthe oryzae. Still, the mechanism of how MoMkk1 regulates autophagy is unclear. Interestingly, we found that MoMkk1 regulates the autophagy protein MoAtg9 through phosphorylation. MoAtg9 is a transmembrane protein subjected to phosphorylation by autophagy-related protein kinase MoAtg1. Here, we provide evidence demonstrating that MoMkk1-dependent MoAtg9 phosphorylation is required for phospholipid …


Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper Feb 2024

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …


Role Of Prmt5 In Ulk1-Mediated Autophagy And Breast Cancer Therapy, Charles Brobbey Dec 2023

Role Of Prmt5 In Ulk1-Mediated Autophagy And Breast Cancer Therapy, Charles Brobbey

MUSC Theses and Dissertations

PRMT5 (Protein arginine methyltransferase 5) is the predominant type II PRMT that monomethylates and symmetrically dimethylates arginine residues of histone and none- histone proteins to regulate diverse cellular processes. PRMT5 overexpression has been implicated in tumorigenesis and other diseases and has gained trac1on as a poten1al an1tumor target with some of its inhibitors being tested in clinical trials. Despite the well- established an1tumor effect of PRMT5 inhibitors, how the efficacy of these inhibitors is regulated is unexplored. We show in this study that autophagy blockage enhances cellular sensi1vity to PRMT5 inhibitor in triple nega1ve breast cancer cells. Both gene1c deple1on …


Efficacy Of Hmj-38, A New Quinazolinone Analogue, Against The Gemcitabine-Resistant Mia-Paca-2 Pancreatic Cancer Cells, Mann-Jen Hour, Fuu‑ Jen Tsai, I-Lu Lai, Je-Wei Tsao, Jo-Hua Chiang, Yu-Jen Chiu, Hsing-Fang Lu, Yu‑ Ning Juan, Jai-Sing Yang, Shih-Chang Tsai Nov 2023

Efficacy Of Hmj-38, A New Quinazolinone Analogue, Against The Gemcitabine-Resistant Mia-Paca-2 Pancreatic Cancer Cells, Mann-Jen Hour, Fuu‑ Jen Tsai, I-Lu Lai, Je-Wei Tsao, Jo-Hua Chiang, Yu-Jen Chiu, Hsing-Fang Lu, Yu‑ Ning Juan, Jai-Sing Yang, Shih-Chang Tsai

BioMedicine

Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIAGR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50, or 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced …


Autophagy-Urea Cycle Pathway Is Essential For The Statin-Mediated Nitric Oxide Bioavailability In Endothelial Cells, Wen-Hua Chen, Bei-Chia Guo, Chia-Hui Chen, Man-Chen Hsu, Chih-Hsien Wang, Tzong-Shyuan Lee Aug 2023

Autophagy-Urea Cycle Pathway Is Essential For The Statin-Mediated Nitric Oxide Bioavailability In Endothelial Cells, Wen-Hua Chen, Bei-Chia Guo, Chia-Hui Chen, Man-Chen Hsu, Chih-Hsien Wang, Tzong-Shyuan Lee

Journal of Food and Drug Analysis

Statins induce nitric oxide (NO) bioavailability by activating endothelial nitric oxide synthase via kinase- and calciumdependent pathways in endothelial cells (ECs). However, their effect on the metabolism of L-arginine, the precursor for NO biosynthesis, and regulatory mechanism have not yet been investigated. In this study, we investigated the role of the autophagy–urea cycle-L-arginine pathway in simvastatin-mediated NO bioavailability in ECs. Griess's assay was used to determine the NO bioavailability. Protein expression was assessed using Western blot analysis. Further, immunocytochemistry was performed to observe autophagosome formation, while conventional assay kits were used to quantify the levels of different intermediate substrates of …


Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston Aug 2023

Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston

Electronic Theses and Dissertations

Loss of myelin causes severe neurological disorders and functional deficits in white matter injuries (WMI) such as traumatic spinal cord injury (SCI). This dissertation is focused on autophagy in OL development and the OL translatome after SCI. Chapter I describes the history of myelin, OL development, and their involvement in neurodegenerative diseases and SCI. The proteostasis network, in particular autophagy, and its contributions to white matter pathology is discussed. It concludes examining advantages and disadvantages of unbiased omics tools, like RiboTag, to study transcriptional/translational landscapes after SCI. Chapter II focuses on autophagy in OPC/OL differentiation, survival, and proper myelination in …


Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe Jun 2023

Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe

Electronic Thesis and Dissertation Repository

Maternal diabetes increases congenital malformations due to teratogenic effects of glucose on the developing embryo. High glucose culture alters preimplantation embryo development and is associated with increased oxidative stress. Apoptosis and autophagy are programmed cell death and survival mechanisms induced by oxidative stress, but their role in preimplantation diabetic embryopathy is poorly elucidated. It was hypothesized that high glucose culture would alter autophagic and apoptotic responses, and that they are dependent on the timing of high glucose culture initiation. Embryos were cultured with 0.2 mM (control) or 25 mM (high glucose) of D-glucose starting from the early (36 hpi) or …


Metformin Induces Autophagy Of Cisplatin-Resistant Human Gastric Cancer Cells In Addition To Apoptosis, Chih-Wun Fang, Jai-Sing Yang, Jo-Hua Chiang, Po-Chuen Shieh, Fuu-Jen Tsai, Chia-Wen Tsai, Wen-Shin Chang May 2023

Metformin Induces Autophagy Of Cisplatin-Resistant Human Gastric Cancer Cells In Addition To Apoptosis, Chih-Wun Fang, Jai-Sing Yang, Jo-Hua Chiang, Po-Chuen Shieh, Fuu-Jen Tsai, Chia-Wen Tsai, Wen-Shin Chang

BioMedicine

Metformin has been used to treat cases of type 2 diabetes mellitus, and mounting studies have shown that metformin can act alone or in synergy with other anticancer agents to achieve anti-cancer efficacies on various types of tumors. However, the role of metformin in either inducing autophagy and cisplatin-resistance of human gastric cancer (GC) cells has never been examined. The study has established a cisplatin-resistant GC cell line and investigated the effects of metformin on inducing autophagy on it. The results demonstrated that treatment with metformin can concentration-dependently suppress the cell viability and cell confluence of cisplatin-resistant GC cells, while …


The Tricarboxylic Acid Cycle As A Central Regulator Of The Rate Of Aging: Implications For Metabolic Interventions, Jonathan M. Borkum May 2023

The Tricarboxylic Acid Cycle As A Central Regulator Of The Rate Of Aging: Implications For Metabolic Interventions, Jonathan M. Borkum

Psychology Faculty Scholarship

Certain metabolic interventions such as caloric restriction, fasting, exercise, and a ketogenic diet extend lifespan and/or health span. However, their benefits are limited and their connections to the underlying mechanisms of aging are not fully clear. Here, these connections are explored in terms of the tricarboxylic acid (TCA) cycle (Krebs cycle, citric acid cycle) to suggest reasons for the loss of effectiveness and ways of overcoming it. Specifically, the metabolic interventions deplete acetate and likely reduce the conversion of oxaloacetate to aspartate, thereby inhibiting the mammalian target of rapamycin (mTOR) and upregulating autophagy. Synthesis of glutathione may provide a high-capacity …


Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley Apr 2023

Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley

Graduate School of Biomedical Sciences Theses and Dissertations

Cells are exposed to an enormous amount of diverse extracellular cues but have a limited arsenal of weapons for protecting and maintaining homeostasis. To overcome these restrictions, nature has engineered proteins that have multiple functions. The pleiotropy of using one protein to carry out a variety of functions allows cells to rapidly execute tailored responses to a diverse set of signals. The Cdk8 kinase module (CKM) is a conserved detachable unit of the Mediator complex predominantly known for its role in transcriptional regulation. The CKM is composed of four proteins, the scaffolding proteins Med13 and Med12, as well as the …


Vitamin D Receptor Mediates Liver Ischemia And Reperfusion Injury By Autophagy-Regulated M2 Macrophage Polarization, Mingming Fang, Chen Zhong Jan 2023

Vitamin D Receptor Mediates Liver Ischemia And Reperfusion Injury By Autophagy-Regulated M2 Macrophage Polarization, Mingming Fang, Chen Zhong

Turkish Journal of Biology

Liver ischemia and reperfusion (IR) injury is the major complication of liver-related operations. Macrophage polarization has an essential effect on the mechanism of liver IR injury. Vitamin D receptor (VDR) has been found to regulate macrophage polarization and alleviate IR injury. Nevertheless, the correlation between VDR and macrophage polarization in liver IR injury has not been clearly elucidated. VDR knockout mice and wild-type littermates underwent partial liver ischemia for 90 min and reperfusion for 6 h. RAW264.7 cells were also used to verify the influence of VDR on macrophage polarization in vitro. VDR activation could promote M2 macrophage polarization and …


Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied Jan 2023

Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied

Master's Theses

Bcl2-associated athanogene-3 (BAG3) is a pro-autophagy co-chaperone that we havepreviously shown localizes to the cardiac sarcomere and is critical for proteostasis and maintenance of normal sarcomeric function. Indeed, BAG3 loss in heart failure (HF) results in accumulation of ubiquitinated sarcomeric proteins, and depressed maximum force generating capacity (Fmax). However, how BAG3 is regulated in the cell is not well understood, with uncertainty about its structure and proteoforms. During our analysis of human heart tissue, BAG3 appears as a “doublet”, with one band at 74 kDa (BAG3-Z) and a second at a higher 85 kDa (BAG3-FL). Previous studies hypothesized the full-length …


Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman Jan 2023

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …


The Protective Impact Of Growth Hormone Against Rotenone-Induced Apoptotic Cell Death Via Acting On Endoplasmic Reticulum Stress And Autophagy Axis, Özge Rencüzoğullari, Selay Tornaci, Yağmur Çeli̇k, Nayat Narot Taş, Pinar Obakan Yerli̇kaya, Eli̇f Damla Arisan, Ajda Çoker Gürkan Jan 2023

The Protective Impact Of Growth Hormone Against Rotenone-Induced Apoptotic Cell Death Via Acting On Endoplasmic Reticulum Stress And Autophagy Axis, Özge Rencüzoğullari, Selay Tornaci, Yağmur Çeli̇k, Nayat Narot Taş, Pinar Obakan Yerli̇kaya, Eli̇f Damla Arisan, Ajda Çoker Gürkan

Turkish Journal of Biology

Human growth hormone (GH) is crucial modulator of cellular metabolisms, including cell proliferation and organ development, by stimulating insulin-like growth factor-1 (IGF-1), which has various functions such as cell proliferation, tissue growth, survival, or neuroprotection. Therefore, GH is implicated as a critical player in the cell and can enhance neurogenesis and provide neuroprotection during the treatment of neurological diseases such as Parkinson's disease (PD). In this study, the neuroprotective role of GH was investigated in rotenone-induced PD models for the first time. Both SH-SY5Y and SK-N-AS neuroblastoma cells were exposed to rotenone to mimic PD pathogenesis as stated in previous …


Rapamycin Inhibits Light-Induced Necrosome Activation Occurring In Wild-Type, But Not Rpe65-Null, Mouse Retina, Chunfeng Lu, Songhua Li, Minghao Jin Dec 2022

Rapamycin Inhibits Light-Induced Necrosome Activation Occurring In Wild-Type, But Not Rpe65-Null, Mouse Retina, Chunfeng Lu, Songhua Li, Minghao Jin

School of Medicine Faculty Publications

PURPOSE. Both photodamage and aberrant visual cycle contribute to disease progress of many retinal degenerative disorders, whereas the signaling pathways causing photoreceptor death remain unclear. Here we investigated the effects of intense photo-stress on (1) necrosome activation in wild-type and RPE65-null mice, (2) interaction of p62/Sequestosome-1 with the necrosome proteins, and (3) the effects of rapamycin on photodamage-induced necrosome activation and retinal degeneration in wild-type mice. METHODS. Dark-adapted rd12 mice and 129S2/Sv mice with or without rapamycin treatment were exposed to 15,000 lux light for different times. Expression levels and subcellular localization of proteins were determined through immunoblot and immunohistochemical …


Elucidating The Mechanisms Underlying How Vmp1 Regulates Inflammatory Responses, Stephanie Zack Oct 2022

Elucidating The Mechanisms Underlying How Vmp1 Regulates Inflammatory Responses, Stephanie Zack

Dissertations

autophagy, inflammation, mitochondria, NLRP3 inflammasome, SERCA, VMP1


The Cryptococcus Neoformans Flc1 Homologue Controls Calcium Homeostasis And Confers Fungal Pathogenicity In The Infected Hosts, Piotr R. Stempinski, Kristie D. Goughenour, Lukas M. Du Plooy, J. Andrew Alspaugh, Michal A. Olszewski, Lukasz Kozubowski Sep 2022

The Cryptococcus Neoformans Flc1 Homologue Controls Calcium Homeostasis And Confers Fungal Pathogenicity In The Infected Hosts, Piotr R. Stempinski, Kristie D. Goughenour, Lukas M. Du Plooy, J. Andrew Alspaugh, Michal A. Olszewski, Lukasz Kozubowski

Open Access Publishing Fund

Cryptococcus neoformans, an opportunistic yeast pathogen, relies on a complex network of stress response pathways that allow for proliferation in the host. In Saccharomyces cerevisiae, stress responses are regulated by integral membrane proteins containing a transient receptor potential (TRP) domain, including the flavin carrier protein 1 (Flc1), which regulates calcium homeostasis and flavin transport. Here, we report that deletion of C. neoformans FLC1 results in cytosolic calcium elevation and increased nuclear content of calcineurin-dependent transcription factor Crz1, which is associated with an aberrant cell wall chitin overaccumulation observed in the flc1Δ mutant. Absence of Flc1 or inhibition …


C60 Hydrofullerene Induced Autophagy And Ameliorated Gfap In H2o2 Treated Human Malignant Glioblastoma U-373 Cell Line, Aryan M. Faraj, Can A. Agca, Victor S. Nedzvetsky, Artem A. Tykhomyrov Aug 2022

C60 Hydrofullerene Induced Autophagy And Ameliorated Gfap In H2o2 Treated Human Malignant Glioblastoma U-373 Cell Line, Aryan M. Faraj, Can A. Agca, Victor S. Nedzvetsky, Artem A. Tykhomyrov

Karbala International Journal of Modern Science

Glioblastoma is one of the most combative astrocytoma that is resistant to chemotherapy and radiotherapy. This resistance makes it very difficult to treat. However, researches have shown that nanoparticles especially C60 hydrofullerene have antioxidant and anticancer activity. The effect of C60 hydrofullerene in cancer has been extensively studied; however, the potential regulation of autophagy and modulation of the Glial Fibrillary Acidic Protein (GFAP) gene has not been addressed in glioblastomas. Glioblastoma U-373 cell was treated with 0.5 µM of C60 hydrofullerene and/or 1 mM of hydrogen peroxide (H2O2) for 24 hours. This study demonstrated that C60 hydrofullerene and H2O2 significantly …


The Regulation Of Atg9a-Mediated Aggrephagy By An Ulk1-Independent Atg13-Atg101 Complex, Joshua Youngs Jun 2022

The Regulation Of Atg9a-Mediated Aggrephagy By An Ulk1-Independent Atg13-Atg101 Complex, Joshua Youngs

Undergraduate Honors Theses

Aggrephagy, a type of autophagy, is an essential cellular process by which protein aggregates are collected and broken down in the lysosome. Protein aggregates are implicated in several diseases including Alzheimer’s disease, diabetes, and cancer. Here, we investigate the ATG13-ATG101 protein complex, a sub-complex of the canonical ULK1 complex whose regulatory role in aggrephagy is not completely understood. We also develop a protein fragment complementation (PFC) assay using the biotin ligase TurboID to study the functions of the ATG13-ATG101 complex with increased specificity. We demonstrate that ATG13 is required for optimal degradation of p62-ubiquitin condensates. We also show that a …


Genome-Wide Transcript And Protein Analysis Highlights The Role Of Protein Homeostasis In The Aging Mouse Heart., Isabela Gerdes Gyuricza, Joel M Chick, Gregory R Keele, Andrew Deighan, Steven C. Munger, Ron Korstanje, Steven P Gygi, Gary Churchill May 2022

Genome-Wide Transcript And Protein Analysis Highlights The Role Of Protein Homeostasis In The Aging Mouse Heart., Isabela Gerdes Gyuricza, Joel M Chick, Gregory R Keele, Andrew Deighan, Steven C. Munger, Ron Korstanje, Steven P Gygi, Gary Churchill

Faculty Research 2022

Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the …


Diurnal Regulation Of Exercise-Induced Myocardial Signaling And Transcription, Charli Aguilar May 2022

Diurnal Regulation Of Exercise-Induced Myocardial Signaling And Transcription, Charli Aguilar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Exercise is well known for its many benefits on the body and most notably the heart. Recent emphasis, and significant resources, have been dedicated to elucidating the molecular mechanisms through which exercise exerts its pluripotent beneficial effects on health and the prevention of disease. A continuous evolution in this field has sought to modulate and optimize exercise in various ways to maximize the benefits. In recent years, a growing appreciation for the impact of circadian rhythms has gained traction and their influence on many essential biological functions have been integrated into exercise physiology (i.e. - chrono-exercise), as well as …


Selective Elimination Of Pluripotent Stem Cells By Pikfyve Specific Inhibitors., Arup R Chakraborty, Alex Vassilev, Sushil K Jaiswal, Constandina E O'Connell, John F Ahrens, Barbara S Mallon, Martin Pera, Melvin L Depamphilis Feb 2022

Selective Elimination Of Pluripotent Stem Cells By Pikfyve Specific Inhibitors., Arup R Chakraborty, Alex Vassilev, Sushil K Jaiswal, Constandina E O'Connell, John F Ahrens, Barbara S Mallon, Martin Pera, Melvin L Depamphilis

Faculty Research 2022

Inhibition of PIKfyve phosphoinositide kinase selectively kills autophagy-dependent cancer cells by disrupting lysosome homeostasis. Here, we show that PIKfyve inhibitors can also selectively eliminate pluripotent embryonal carcinoma cells (ECCs), embryonic stem cells, and induced pluripotent stem cells under conditions where differentiated cells remain viable. PIKfyve inhibitors prevented lysosome fission, induced autophagosome accumulation, and reduced cell proliferation in both pluripotent and differentiated cells, but they induced death only in pluripotent cells. The ability of PIKfyve inhibitors to distinguish between pluripotent and differentiated cells was confirmed with xenografts derived from ECCs. Pretreatment of ECCs with the PIKfyve specific inhibitor WX8 suppressed their …


Sirna-Mediated Stathmin1 Silencing Inhibits Proliferation Of Prostate Carcinoma Cell Line, Asude Aksoy, Safi̇ye Selcen Vi̇cdanli, Ebru Önalan, Ahmet Tektemur, Gökhan Artaş, Asuman Orhan Varoğlu, Mustafa Koç Jan 2022

Sirna-Mediated Stathmin1 Silencing Inhibits Proliferation Of Prostate Carcinoma Cell Line, Asude Aksoy, Safi̇ye Selcen Vi̇cdanli, Ebru Önalan, Ahmet Tektemur, Gökhan Artaş, Asuman Orhan Varoğlu, Mustafa Koç

Turkish Journal of Biology

Stathmin1 (STMN1) has been proposed as a possible prognostic marker and a potential therapeutic target for some cancers. We aimed to analyze the changes in autophagy, invasion, apoptosis-related genes in prostate cancer (PCa) cell line (PC-3), after small interfering RNA (siRNA)-mediated STMN1 silencing, and also the relationships of STMN1 expression, clinicopathological parameters, and survival (OS) in PCa cases. The STMN1 expressions were analyzed, immunohistochemically, in formalin-fixed paraffin-embedded 75 PCa and 15 benign prostatic hypertrophy (BPH) tissues. The correlation between the levels of expression STMN1, clinicopathological features, and OS was determined in PCa cases. The siRNA-mediated STMN1 incubated PC-3 cells were …


Palmitic Acid Declines Glucose Uptake In Hepg2 Cells Via Modulating Phosphoglucomutase 1 To Repress Phosphatidylinositol 3 Kinase/Protein Kinase B And Jnk Pathways Via Inducing Microrna-124-3p, Linghui Zhang, Shengli Zhang Jan 2022

Palmitic Acid Declines Glucose Uptake In Hepg2 Cells Via Modulating Phosphoglucomutase 1 To Repress Phosphatidylinositol 3 Kinase/Protein Kinase B And Jnk Pathways Via Inducing Microrna-124-3p, Linghui Zhang, Shengli Zhang

Turkish Journal of Biology

Diabetes resulting from insufficient insulin secretion or insulin resistance (IR) is a highly prevalent metabolic disease. Since microRNAs have been linked with elevated IR, the current research hypothesized that miR-124-3p has a role in IR and the establishment of IR and type 2 diabetes (T2DM). The study aimed to explore the molecular mechanisms of miR-124-3p which influence IR leading to T2DM establishment. HepG2 cells were cultured in vitro, and palmitic acid (PA) was used to construct the IR cell model. In the IR model, transfection of miR-124-3p or phosphoglucomutase 1 (PGM1) linked plasmids were transfected into HepG2 cells. RT-qPCR was …


Acceleration Of Slow Autophagy Flux Induced By Arabinofuranosyl Cytidine Improves Its Antileukemic Effectiveness In M-Nfs-60 Cells, Salwa Fouad, Gamal Elsokkary, Abo Bakr Abdel Shakor Jan 2022

Acceleration Of Slow Autophagy Flux Induced By Arabinofuranosyl Cytidine Improves Its Antileukemic Effectiveness In M-Nfs-60 Cells, Salwa Fouad, Gamal Elsokkary, Abo Bakr Abdel Shakor

Turkish Journal of Biology

Arabinofuranosyl cytidine (AraC) is an analog of deoxycytidine used as an anticancer drug for leukemic patients. The effective dose always produces severe complications. The present study investigated the modulation of autophagy and its impact on the cytotoxicity of AraC toward murine myelogenous leukemia cells (M-NFS-60). Autophagy was inhibited by NH4Cl or Bafilomycin A1 or enhanced by amino acid starvation, glucose starvation, mild hyperthermia (41 °C), or rapamycin (Rap). Cells were treated with different concentrations, 0 to 2 µM, of AraC in the presence or absence of autophagy modulators. AraC-induced apoptosis is combined with autophagy, especially at lower concentrations. This autophagy …


Calmodulin Like 38 Is Required For Autophagy Of Hypoxia-Induced Cytoplasmic Rna Granules In Arabidopsis Thaliana, Sterling Field Dec 2021

Calmodulin Like 38 Is Required For Autophagy Of Hypoxia-Induced Cytoplasmic Rna Granules In Arabidopsis Thaliana, Sterling Field

Doctoral Dissertations

In response to the energy crisis resulting from submergence stress and hypoxia, the model plant Arabidopsis thaliana limits non-essential mRNA translation, and accumulates cytosolic stress granules. Stress granules are phase-separated mRNA-protein particles that partition transcripts for various fates: storage, degradation, or return to translation after stress alleviation. Another response by the plant cell to low oxygen stress is the induction of the turnover pathway autophagy. Stress granule regulation by autophagy occurs by a ‘granulophagy’ pathway in yeast and mammalian systems through which parts or whole stress granules are degraded. Whether this occurs in plants has not been investigated.

A connection …


Role Of Autophagy In Acridocarpus Orientalis-Induced Anti-Breast Cancer Activity, Suhib Hisham Ahmed Saeed Altabbal Nov 2021

Role Of Autophagy In Acridocarpus Orientalis-Induced Anti-Breast Cancer Activity, Suhib Hisham Ahmed Saeed Altabbal

Theses

Breast cancer is the most frequently diagnosed cancer in women worldwide. Triple Negative Breast Cancer (TNBC), which lacks the expression of the hormonal Estrogen Receptor (ER) and Progesterone Receptor (PR), and the amplification of Human Epidermal Growth Factor Receptor 2 (HER2), is not responsive to the hormonal therapy. Therefore, chemotherapy and radiotherapy, which cause severe side effects, are the current available choices to treat TNBC. Hence, there is an urgent need to find new therapeutic choices for TNBC. It is estimated that 50% of all drugs in clinical use during the 21st century are natural products and plants derived. …