BIO 590 San Diego State University Erythropoietin Hormone and Receptors Report

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Your report will have Your name, title, abstract (300 to 500 words), introduction (why is it important and focus), key information (figures, illustrations, data), discussion, information sites and publications.2)I have an outlined what information that will be included for both the hormone and receptor(s) to complete report. This includeskey information that can be conveyed as text, figures, illustrations or tables. I find organizing information is easiest withPPT. You can submit-upload the final report as PowerPoint or Word doc. If you are using Google Docs there will be a place for a URL link.3)I have included trusted online information sites that are appropriate for the report: A) Wikipedia;B) PubMed; C) NIH/Protein; D) Google Images; E) KEGG Pathways; F) MedlinePlus; G) Mayo Clinic and other sites.4)In addition, at least 5 scientific references from PubMed will be included. You should download free PDF copies of the articles,read them and include the first page (PDF) in your reports.5)By reviewing this information and literature you will select the final emphasis of your hormone report. 6)I anticipate each report will be between 12 to 25 pages. There will be a CANVAS module set up for submission.

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Due date: Nov 17th at 11:59PM. The point of the Bio590 hormone report (Fall 2020) is designed to expand you research and comprehension skills… A) The physiology-base and homeostatic processes of the human body that are regulated and coordinated by the release of key B) C) D) E) signaling factors (hormones, neurohormones, neurotransmitters, etc..). Expand your working knowledge on how receptor-ligand information results in the integrated responses of target tissues. Understand how altering these ligand-receptors interactions may influence acute and long-term health and disease processes. The report will also serve as a bridge between your understanding of molecular-biochemial concepts and human physiology. My goal is to have everyone to become proficient at accessing, researching and critically evaluating appropriate scientifically based source material. Since we will be working with virtual format for the foreseeable future, you will use source material from trusted online information sites. Using information from sites including FACEBOOK or SNAPCHAT 1) Your report will have Your name, title, abstract (300 to 500 words), introduction (why is it important and focus), key information 2) 3) 4) 5) 6) (figures, illustrations, data), discussion, information sites and publications. I have an outlined what information that will be included for both the hormone and receptor(s) to complete report. This includes key information that can be conveyed as text, figures, illustrations or tables. I find organizing information is easiest with PPT. You can submit-upload the final report as PowerPoint or Word doc. If you are using Google Docs there will be a place for a URL link. I have included trusted online information sites that are appropriate for the report: A) Wikipedia; B) PubMed; C) NIH/Protein; D) Google Images; E) KEGG Pathways; F) MedlinePlus; G) Mayo Clinic and other sites. In addition, at least 5 scientific references from PubMed will be included. You should download free PDF copies of the articles, read them and include the first page (PDF) in your reports. By reviewing this information and literature you will select the final emphasis of your hormone report. I anticipate each report will be between 12 to 25 pages. There will be a CANVAS module set up for submission. Primary information to include on the “Hormone” using insulin as an example. Hormone (name) Insulin Review of homeostatic or regulatory impact on cells, tissues and whole organism. This gene encodes insulin, a peptide hormone that plays a vital role in the regulation of carbohydrate and lipid metabolism. After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the Reference Sources: Wikipedia, Google images, Medical insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant sites, Textbook, publications alleles with phenotypic effects have been identified, including insulindependent diabetes mellitus, permanent neonatal diabetes diabetes mellitus, maturity-onset diabetes of the young type 10 and hyperproinsulinemia. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. Information Type or Class of Hormone Peptide, Steroid, Catecholamines, Amino Acid, Eicosnoids Hormone, Neurohormone, Neurotransmitter Chemical Structure or AA sequence Chemical, KEGG Pathway Picture Amino acid sequence Primary AA sequence Cellular Pathway RER and processed in TransGolgi Network Cell type production Pancreatic islets beta cells Secretion Pathway Vesicular transport and fusion Physiological Stimulation Elevated blood glucose and amino acid levels Autocrine, Paracrine, Endocrine, Multiple or other Endocrine Synthesis Secretion - Release Type of functional endocrine signal Scientific references and other human conditions, health and disease related factors. Primary information to include on the “Receptor(s)” using insulin receptor as an example. Receptor(s) Name Signal Transduction Pathways Disorders associated with too much “signaling” Disorders associated with too little “signaling” Tissue Responses Drugs Insulin Receptor Amino Acid sequence(s) Structure Type and Acute impact Type and Long-term impact yes yes Nervous (nerves, glia) Circulatory (heart, blood, vasculature) Adipose (viseral, subcutanious, marrow) Digestive (stomach, liver, pancreas) Muscoloskeletal (muscle, bone, connective) Urinary (kidney, blatter) Respiratory (lung, bronchia) Endocrine (glands and other tissues) Immune (WBCs, innate, acquired) Reproductive (male, female) Agonist (mechanism) Antagonist (mechanism) Kinase signaling, ion channels, etc…. Enzyme modulation, Transcriptional changes, etc … hypoglycemia, Insulin shock, seizure, coma Type 1 diabetes, frequent urination, thirst Yes with more details yes yes yes yes yes yes yes yes yes antibodies? S961 peptide? Other human conditions and additional health and disease related factors: Working Rubric for grading the report: Hormone-based information (8 pts). Information with +3 paragraph focused written report. Receptor(s)-based information (8pts). Information with +3 paragraph focused written report. Scientific-Medical based references that reflect the focus of your report (3 pts). Highlighted information you found interesting and consideration of future directions (2pts). Report esthetics: concise, well written and organized format (2pts). Individual assigned secreted factor or hormone. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 Student Rawan Alabdali Abdulahad Albaashiki Collin Allen Nina Alobaidi Abdulaziz Alsharad Joshua Avila Mary Bandar Kaily Beckner Rebekah Belasco Cole Berlioz Amanda Buck Audrea Cain Adam Camp Alexis Cartwright Grant Cassidy Juneau Catalano Sally Chen Faith Corpus Joshua Cure Noah Danieli Justin Dela Cruz Lindsay Doron Tory Edwards Rachel El-Jof Monica Esquer Pia Garewal Megan Garvin Leila Golgolab Larsa Goro Emily Gutierrez Cameron Hallisey Reem Hanna Al-Kass Heather Erika Heintzen Nancy Her Maryam Herfi Tyler Hernandez Austin Hirmiz Yasameen Jasim Secreted Factor (hormone) Insulin-like growth factor Serotonin Vasoactive intestinal peptide Thyrotropin-releasing hormone Thrombopoietin Somatostatin Secretin Renin Relaxin Prolactin-releasing hormone Prolactin Pituitary adenylate cyclase-activating peptide Parathyroid hormone Endorphins Oxytocin Osteocalcin Orexin Motilin Melanocyte stimulating hormone Luteinizing hormone Lipotropin Leptin Insulin-like growth factor (or somatomedin) Inhibin Human placental lactogen Human chorionic gonadotropin Hepcidin Guanylin Growth hormone-releasing hormone Growth hormone Gonadotropin-releasing hormone Glucagon Ghrelin Gastrin Gastric inhibitory polypeptide Galanin Follicle-stimulating hormone Erythropoietin 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 Student Secreted Factor (hormone) Nicole Johnson Bridget Kelleher Sarah Kousba Jennifer Kutzler Nathanael Larson Avory Leander Felicia Mallillin Alex Mann Rachel Margolis Jeanette Marino Mikayla Marrin Sarah McHenry Ryan Murphy Clara Neal Hannah Nguyen Kaylee Nguyen Kelvin Nguyen Areeba Paracha Rita Raho Vernon Rayo Emma Roberts Kendall Rollin Daniel Rouel Elle Joy San Juan Clarissa Savko Serena Shaar Meina Shammas Gina Torabzadeh Tan Trinh Erica Tsung Samuel Van Zuthem Taylor Warch Zachary White Weston Willard Miena Williams Lule Yan Sarah Yoshioka Wella Yung Brain-derived neurotrophic factor (BDNF) Endothelin Cortistatin Corticotropin-releasing hormone Cholecystokinin Calcitonin Atrial natriuretic peptide (or atriopeptin) Antidiuretic hormone (or vasopressin, arginine vasopressin) Anti-MŸllerian hormone (or MŸllerian-inhibiting factor or hormone) Angiotensinogen and angiotensin Amylin (or Islet Amyloid Polypeptide) Adrenocorticotropic hormone (or corticotropin) Dehydroepiandrosterone Dihydrotestosterone Aldosterone Estradiol Cortisol Progesterone Testosterone Calcitriol (1,25-dihydroxyvitamin D3) Calcidiol (25-hydroxyvitamin D3) Ciliary neurotrophic factor (CNTF) Leukemia inhibitory factor (LIF) Brain-derived neurotrophic factor (BDNF) Macrophage colony-stimulating factor (M-CSF) Granulocyte colony-stimulating factor (G-CSF) Granulocyte macrophage colony-stimulating factor (GM-CSF) Epidermal growth factor (EGF) Interleukin-6 (IL-6) Interleukin-1 (IL-1) Tumor necrosis factor (TNF) Thromboxane Leukotriene D4 (LTD4) prostaglandin I2 (prostacyclin; PGI2) prostaglandin D2 (PGD2) Interleukin 8 (IL-8) Adiponectin Fibroblast growth factor (FGF) https://www.wikipedia.org/ A good starting point… https://www.ncbi.nlm.nih.gov/protein/ For protein sequences and other additional information… https://www.ncbi.nlm.nih.gov/protein/ https://www.ncbi.nlm.nih.gov/protein?term=blast insulin preproprotein [Homo sapiens] FASTA Sequence NCBI Reference Sequence: NP_000198.1 [FASTA] 110 aa Signal peptide RER Beta insulin (C=cystine bond) C Peptide Alpha insulin MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAEDLQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN https://pubmed.ncbi.nlm.nih.gov/ PDF of first page. Can J Diabetes 41 (2017) 108–113 You will cite and provide at least 5 references for your report that focuses on your select hormone and receptor. These will be your primary sighted references in the report. Contents lists available at ScienceDirect Canadian Journal of Diabetes journal homepage: w w w. c a n a d i a n j o u r n a l o f d i a b e t e s . c o m 2015 CDA Lifetime Achievement Award Winner Review Insulin Signalling: The Inside Story Barry I. Posner OC, CQ, MD, FRSC, FRCPC, FACP * Department of Medicine, McGill University Hospital Research Institute, Montreal, Quebec, Canada a r t i c l e i n f o a b s t r a c t Article history: Received 8 June 2016 Received in revised form 14 July 2016 Accepted 15 July 2016 Insulin signalling begins with binding to its cell surface insulin receptor (IR), which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently autophosphorylated and activated to tyrosine phosphorylate key cellular substrates that are essential for entraining the insulin response. Although IRK activation begins at the cell surface, it is maintained and augmented following internalization into the endosomal system (ENS). The peroxovanadium compounds (pVs) were discovered to activate the IRK in the absence of insulin and lead to a full insulin response. Thus, IRK activation is both necessary and sufficient for insulin signalling. Furthermore, this could be shown to occur with activation of only the endosomal IRK. The mechanism of pV action was shown to be the inhibition of IRK-associated phosphotyrosine phosphatases (PTPs). Our studies showed that the duration and intensity of insulin signalling are modulated within ENS by the recruitment of cellular substrates to ENS; intra-endosomal acidification, which promotes dissociation of insulin from the IRK; an endosomal acidic insulinase, which degrades intra-endosomal insulin; and IRK-associated PTPs, which dephosphorylate and, hence, deactivate the IRK. Therefore, the internalization of IRKs is central to insulin signalling and its regulation. © 2016 Canadian Diabetes Association. Keywords: endosomal acidic insulinase endosomes insulin receptor phosphorylation phosphotyrosine phosphatase tyrosine kinase r é s u m é Mots clés : insulinase endosomique acide endosomes récepteur de l’insuline phosphorylation phosphotyrosine phosphatase tyrosine kinase La signalisation de l’insuline commence par la liaison de l’insuline à son récepteur (IR) situé à la surface des cellules, soit la tyrosine kinase. La kinase du récepteur de l’insuline (KRI) s’est subséquemment autophosphorylée et activée vers les principaux substrats cellulaires de la tyrosine phosphorylée qui sont essentiels au déclenchement de la réponse à l’insuline. Bien que l’activation de la KRI commence à la surface des cellules, elle est maintenue et augmentée à la suite de l’internalisation du système endosomal (SEN). Il a été découvert que les composés de peroxovanadium (pV) activent la KRI en l’absence d’insuline et mènent à une réponse insulinique complète. Par conséquent, l’activation de la KRI est nécessaire et suffisante à la signalisation de l’insuline. De plus, il pourrait être démontré qu’elle apparaît avec l’activation de la KRI endosomale seulement. Il a été démontré que le mécanisme de l’activité du pV est l’inhibition des phosphotyrosines phosphatases (PTP) associées à la KRI. Nos études ont montré que la durée et l’intensité de la signalisation de l’insuline sont modulées au sein du SEN par le recrutement de substrats cellulaires du SEN; l’acidification intra-endosomale, qui favorise la dissociation de l’insuline de la KRI; une insulinase endosomique acide, qui dégrade l’insuline dans les endosomes; les PTP associées à la KRI, qui déphosphorylent et, donc, désactivent la KRI. Par conséquent, l’internalisation des KRI est essentielle au déclenchement de la signalisation de l’insuline et à sa régulation. © 2016 Canadian Diabetes Association. Introduction Type 2 diabetes mellitus is characterized by both resistance to the action of insulin and defects in insulin secretion. The former has been an important motivating factor in the exploration of insulin * Address correspondence to: Barry I. Posner, OC, CQ, MD, FRSC, FRCPC, FACP, Department of Medicine, McGill University Hospital Research Institute, Glen Bloc E, Room E02.7248, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada. E-mail address: barry.posner@mcgill.ca 1499-2671 © 2016 Canadian Diabetes Association. http://dx.doi.org/10.1016/j.jcjd.2016.07.002 action on its target tissues. By 1970, the notion that insulin and other peptide hormones interacted with specific cell surface receptors was established. Thus, incubating cells with 125I-insulin and increasing quantities of unlabelled insulin defined receptors for insulin as cell surface binding sites of high affinity (~10−9 M) and specificity (1). Shortly thereafter, my colleagues and I recognized that the demonstration of specific binding sites (i.e. receptors) in any tissue was a new way of defining hormone target tissues. We demonstrated insulin receptors in the classic target tissues (liver, fat and muscle) but also in a range of other tissues not previously regarded as insulin targets (e.g. placenta and brain) (2). To define the selection of images use Hormone name and protein and synthesis and receptor and signaling Google Images Website. https://www.google.com/imghp?hl=EN https://www.kegg.jp/kegg-bin/highlight_pathway?scale=1.0&map=map04913&keyword=testosterone insulin receptor isoform Long preproprotein [Homo sapiens] NCBI Reference Sequence: NP_000199.2 [FASTA Sequence Format] 1382 aa MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHL KELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECLGNCSQPDDPTKCVACR NFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQGCHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEAN LGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSYIRTSFDKI LLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIIL KWKPPSDPNGNITHYLVFWERQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGTGAEDPRPSRKRRSLGDVG NVTVAVPTVAAFPNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEEL HLCVSRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSREKIT LLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNA KKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMR PTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSNPS Gene expression pattern of the INSR gene.
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Running Head: HORMONE REPORT

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Report about Erythropoietin Hormone and Receptors
Name
Institutional Affiliation
Course
Date

HORMONE REPORT

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Abstract

This report explores how hormones, neurotransmitters, and neurohormones released by
the human body, regulate and coordinate homeostatic processes. All these signaling factors are
essential for the proper physiological functioning of the human body. We will examine in detail
how target tissues respond to receptor-ligand information. We shall further look into how any
altercation of these ligands' interaction- receptors affects one's health and disease processes both
acutely and long- term. The major areas covered in this report are hormones and receptors. We
shall use an example of one hormone and receptors to explore the correlation between normal
physiological processes of the body and molecular, biochemical concepts.
The report includes well researched and evaluated concepts supported by relevant sources
that are up to date and trustworthy. These sources are mainly online information sites with
information relevant to our study. The sources used include Wikipedia, PubMed, NIH/Protein,
Medline Plus, Mayo clinic, KEGG pathways, and google images. In this case, the hormone we
will be analyzing is Erythropoietin. We will review the class to which the hormone belongs, with
the example of insulin. We shall equally examine the regulatory and homeostatic impact on an
organism's tissues and cells. We shall also use insulin receptors to analyze disorders related to
little or too much Signaling.
The report will also include charts and diagrams of the various concepts discussed. These
include those of protein sequences. There are additional images that give additional information
about erythropoietin hormone concerning protein synthesis and receptor Signaling. Additional
charts showing the expression of genes are also included in the report.
Keywords – receptors, hormones, insulin, homeostatic, physiological

HORMONE REPORT

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Introduction

This study's major focus is to understand in detail the concepts surrounding the
erythropoietin hormone and receptor. It is necessary to examine these two working principles
because of major homeostatic processes in the human body. It is also necessary to understand the
effect of high or low erythropoietin content in the bloodstream as it is useful in primary
regulatory body functions. This report will analyze the structure, effects, and working principles
of erythropoietin hormone and receptor.
Erythropoietin Hormone
The erythropoietin hormone is a glycoprotein cytokine predominantly secreted by
specific cells found in the kidney. Its primary purpose is to stimulate the production of sufficient
erythrocytes by the bone marrow's stem cells. It also serves to protect the red blood cells from
destruction (Mocini et al., 2007). This serves to aid in several physiological and homeostatic
functions of the body. The diagram below shows how a low red blood cell count in the body
stimulates the kidney to produce Erythropoietin hence increasing the synthesis of erythrocytes.

The cytokine erythropoietin (EPO) invigorates the production of billions of erythrocytes.
After production into the bloodstream, its primary destination is the progenitor cells of the
erythroid glands located within the bone marrow to conduct erythropoiesis, producing the
erythrocytes. EPO works to stimulate proliferation, differentiation, and cell survival by acting as

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a binder to the erythroid progenitor cells' surface receptors. Studies have shown that if a
knockout of the EPO receptor occurs, it can cause embryonic death due to severe anemia.
Homeostatic and regulatory impact on organisms
Erythropoietin (EPO) is a useful hormone for maintaining body tissues, stress response,
and metabolism. It is a hormone coded into 193 amino acid polypeptides with carboxyl-terminal
arginine and a 27 amino acid canonical leader sequence. It belongs to the hematopoietic cytokine
family and is often associated with its structural similarity to the growth hormone. Some of its
standard regulatory functions include:


Erythropoietin regulation in the critical liver and adult kidney



Use of Hypoxia-Induced Factor to regulate EPO gene expression.

EpoR is expressed in particular non-hematopoietic tissues at the peak in erythroid
progenitor cells that provide EPO responses. Non-hematopoietic expression of EpoR and the
plausible outcome of EPO activity obtained through models, including vascular endothelium to
instigate nitrogen oxide production regulating vascular tone (Zhang et al., 2014). It also
facilitates skeletal muscle myoblasts' production to promote wound healing. Moreover, it
stimulates the heart to protect against ischemic injury. All these in conjunction with EPO being a
multi-functional cytokine whose primary function is to regulate red blood cell production in the
bone marrow.
EPO is equally known for regulating inflammation. It is stimulated whenever an
inflammation occurs in the body. It acts upon the inflammation by inhibiting inflammatoryinducing cytokine production and endothelial cell response and by reducing immune cell
response to the affected area. This property comes into use for cardiovascular system treatments

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and the central nervous system. It is also applicable to the gut and liver. It is used in combination
with oral iron improved anemia to treat inflammatory bowel disease with anemia refractory.
Erythropoietin is known to minimize Insulin resistance in adipocytes. EPO being a
glycoprotein, has been widely used in treating anemia caused by tumors and chronic kidney
diseases. EPO is active in many body tissues. These include renal, endothelium, cardiovascular
tissues, nerves, and muscle tissues in response to metabolic and muscle stress. However, the role
of the hormone and its receptors in skeletal muscles have not yet been fully explained to date.
The uncertainty arises from evidence suggesting that C2C12 myoblasts, when treated with EPO,
indicate elevated JAK2, STAT5, and AKT. This similarity is associated with signaling responses
observed in neural cells.
Type two diabetic organisms can be treated with the help of Erythropoietin.
Administering EPO can reduce insulin resistance greatly and also activate its related receptor
erythropoietin receptor (EPOR). Moreover, using EPO treatment to increase glucose intolerance
in humans has proven to be a huge success (Pan et al., 2017). The study's overall result to
investigate this concept showed that EPO= EPOR treatment is beneficial to enhance glues uptake
in the body and activate downstream signaling molecules such as P13K, AKT IRS-1. And
Besides, it improves autophagy and minimizes apoptosis in skeletal muscle that is type two
diabetic.

Summary of Homeostatic and Regulatory functions of EPO

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Chemical Structure or AA sequence
As earlier mentioned, Erythropoietin (EPO) is a glycoprotein. It has over 30,400 Daltons
of glycoprotein, with 165 amino acids secreted primarily in the kidney. Some minimal contents
of EPO are produced in the liver for the purpose of erythrocytosis regulation. Its well- versed
function is acting on erythroid precursor cell at the colony-forming units-erythroid stage, thus
aiding apoptosis inhibition. EPO activates at least three specific intracellular signaling pathways
by binding on a specific membrane receptor. These intracellular pathways include Ras-mitogenactivated protein kinase, phosphatidylinositol 3-kinase/ protein kinase B, and some members of
the signal transducers and activators of the transcription family.

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The EPO gene is situated on the 7th chromosome. It is composed of four introns and five
exons, and an amino acid chain of 193 bases forms the transcriptional product of the gene. When
gene translation takes place, the chain is altered and modified to 166 amino acids. The 27 amino
acid leader sequence that has been split is mostly made of hydrophobic amino acids. The final
length of the chain is 165 amino acids. This length is achieved after translation is complete, and
the C-terminus has lost its final arginine residue. The total weight of the glycoprotein is 30 kDa,
with the peptide backbone weighing 18 kDa. EPO, as a glycoprotein, contains sulfur content in
its structural composition. This sulfur of the cysteine residues combines to form disulfide bonds
that help maintain the EPO's structure. The EPO's structure comprises four alpha helixes, namely
A to D. These helixes are interconnected one to another, thus forming the normal EPO structure.
Structure of Erythropoietin with 165 Amino Acids

HORMONE REPORT
Amino acid substitutions in the extracellular domain of the human EPO receptor

KEGG Pathway for cytokine to cytokine receptor interaction

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Synthesis
Under normal conditions, in the absence of anemia, Erythropoietin levels in the blood are
quite low. The volume of EPO content in the blood is around ten mU/mL. However, when the
oxygen reaching body tissues reduces, and hypoxia occurs, EPO production can rise to about
10 000 mU/mL in blood. In adults, the organs responsible for the synthesis of EPO are the
interstitial cells in the renal cavity's peritubular capillary bed (Pan et al., 2017). Nevertheless,
studies have shown evidence of additional amounts being produced by the brain and the liver.
The dimeric protein complex in charge of how the body responds to low oxygen concentration is
called the Hypoxia- Inducible Factor (Mocini et al., 2007). They are the transcription factors for
EPO and are proteasomal and hydroxylated digested in oxygen and iron. Gata2 inhibits the
promoter region for EPO during normoxia. But during hypoxia, the levels decrease during and
give room for the promotion of EPO production. According to medical health researchers,
regulation of EPO amounts synthesized relies on a feedback mechanism that measures iron and
oxygenated blood availability.
Stages of erythroid differentiation and oxygen-dependent feedback loop regulated
by kidney EPO

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Type of Functional Endocrine signal
Erythropoietin (EPO) has similar functionality as a regular endocrine hormone. This is
because it affects target cells in the bone marrow by interacting with specific cell-surface
receptors. In this case, the cell surface receptor consists of two EPOR molecules.
Erythropoietin Receptor
The receptor discussed in this report is the erythropoietin receptor (EpoR). The EpoR is
located on the erythroid progenitor cells. It is a protein in the human body encoded by
the EPOR gene. It belongs to the family of cytokine receptors and pre-exists as dimers. When
bound with a 30 kDa ligand erythropoietin (EPO), they change their homodimerized state. EpoR
has a single carbohydrate chain and is a peptide. It contributes to approximately 56-57 kDa of the
protein found on EPO responding cells' surface. When the homodimerized state changes, Jak2
kinases are autophosphorylated. The receptor depends on these Jak2 kinases for all their intrinsic
kinase activity as it does not possess its own.

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The known function of EpoR is to prevent apoptosis by attaching to the EPO. It
achieves this by promoting proliferation and rescue of erythroid progenitors. However, vitro
rescue experiments have revealed that the determined three-dimensional structure of the EPOR
can cause dimerization of the EPOR domain together with a biologically active 20 amino acid
peptide. EPO activates the JAK2-STAT5 pathway and two tyrosine residues in the cytoplasmic
domain of EPOR, which are necessary to activate STAT5. The physiologic role of STAT5 in
erythroid cell proliferation and differentiation is still subject to debate among many scientists to
date.
Structure of the erythropoietin receptor
The Erythropoietin belongs to the class I cytokine receptor. It forms a complex structure
that is homodimeric, heterodimeric, or heterotrimeric containing a WSXWS motif in the
extracellular domain. It also has a single transmembrane domain. It is the homodimeric receptor
complex to which the EPO binds, thus bringing the JAK2 kinases closer to allow JAK
phosphorylation of the receptor, transphosphorylation, and phosphorylation and activation of
STAT and other downstream signaling pathways.
The diagram below shows the Erythropoietin receptor and signaling pathways. It has
clearly outlined the structure of the receptor dimer. The various docking sites for several
intracellular proteins have been marked with P and linked with the black-dotted arrow to
individual pathway components. Positive interactions are presented with full black arrows and
negative interactions with dotted red.

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Signal Transduction pathways
Signal transduction via the erythropoietin receptor is initiated by ligand binding, which
causes the dimerization of EPOR monomers. The EpoR activates the activator of transcription
(STAT) pathway and the Janus-activated kinase (JAK). The kinase that the EpoR predominantly
associates with is the JKA2. It serves as a protein transporter for the EpoR to the endoplasmic
reticulum’s plasma membrane.
Multiple signaling pathw...


Anonymous
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