Ch1 The Cell Flashcards
Binding site for transcription factors
Promoter and enhancer regions
RNAs that are never translated but regulate gene expression through a variety of mechanisms . Includes miRNAs and lncRNAs
Noncoding regulatory RNAs
Non-protein coding sequence that make up more than a third of the genome. Can move around the genome (“jumping genes”) resulting in a variable copy number and positioning even among closely related species
Mobile genetic elements (e.g. transposons)
The two most common forms of DNA variation in the human genome
Single nucleotide polymorphisms (SNPs) and copy number variations (CNVs)
Variants at single nucelotide positions; almost always biallelic (i.e. only 2 choices existing at a given site within the population e.g. A or T)
Single nucleotide polymorphisms (SNPs)
Form of genetic variation consisting of different numbers of large contiguous stretches of DNA
Copy number variations (CNVs)
Non-coding RNAs that modulate translation of target messenger RNAs.
Action results in post-transcription silencing by cleavage or translational repression of mRNA
miRNAs
Non-coding RNA that modulates gene expression by several mechanisms including:
A) facilitating TF binding and promoting gene activation
B) bind TF to inhibit transcription
C) promote chromatin modification
D) act as scaffolds for assembly of protein complexes
Long non-coding RNAs (lncRNAs)
Nonrandom association of alleles of different loci
(e.g. SNPS may be useful markers if co-inherited with a disease associated polymorphism as a result of physical proximity)
Linkage disequilibrium
Contain catalase, peroxidase, and other oxidative enzymes. Play a specialised role in the breakdown of very long chain fatty acids, generating hydrogen peroxide in the process
Peroxisomes
“disposal” complexes that degrade denatured or otherwise “tagged” cytosolic proteins
proteasomes
intracellular organelles containing degradative enzymes that permit digestion of a wide range of macromolecules
Lysosomes
3 major classes of cytoskeletal proteins
- Actin microfilaments
- Intermediate filaments
- Microtubules
5-9nm diameter fibrils formed from the globular protein actin (G-actin)
Actin filaments
10nm diameter fibrils that comprise a large and heterogeneous family that includes keratin proteins and nuclear lamins
Predominantly form ropelike polymers that do not usually actively reorganise
Intermediate filaments
25nm thick fibrils composed of noncovalently polymerised alpha and beta tubulin dimers organised into hollow tubes
Extremely dynamic with + and - ends
Microtubules
Form the core of primary cilia
Microtubules
Seal adjacent epithelial cells together to create a continuous barrier that restricts the paracellular movement of ions and other molecules
Occluding (tight) junctions
Mechanically attach cells and their cytoskeletons to others cells or the ECM
Anchoring junctions (adherens junctions and desmosomes)
In this form of anchoring junction, the transmembrane adhesion molecules are associated with intracellular actin microfilaments through which they can also influence cell shape and/or motility
Adherens junctions
In this form of anchoring junction, the cadherins are linked to intracellular intermediate filaments, allowing extracellular forces to be mechanically communicated (and dissipated) over multiple cells
Desmosomes
In this form of anchoring junction, integrins are the transmembrane connector proteins which attach to intermediate filaments and link the cytoskeleton to the ECM
Hemidesmosomes
Junctions that permit the diffusion of chemical or electrical signals from one cell to another
Communicating (gap) junctions
Proteins and lipids destined for other organelles or extracellular transport are shuttled here from the RER
Golgi apparatus
Relatively sparse in most cells and primarily exists as the transition zone extending from RER to generate transport vesicles that carry newly synthesised proteins to the Golgi apparatus
More conspicuous in cells synthesising steroid hormone (e.g adrenals) or that catabolise lipid soluble molecules (e.g hepatocytes)
Smooth endoplasmic reticulum
Responsible for sequestering intracellular calcium
Smooth endoplasmic reticulum
These enzymes are initially synthesised in the ER lumen and then tagged with mannose-6-phosphate (M6P) within the Golgi apparatus
Lysosomal enzymes
Degrade cytosolic proteins such as denatured or misfolded proteins as well as any other macromolecule whose lifespan needs to be regulated (may proteins are labelled for destruction by ubiquitin)
Proteasomes
Phenomenon of rapidly dividing cells increasing their uptake of glucose and glutamine and switching to aerobic glycolysis
Warburg effect
Growth factor produced by activated macrophages, salivary glands, keratinocytes…
Mitogenic for many cell types’ stimulates epithelial cell migration; stimulates formation of granulation tissue
EGF
Produced by activated macrophages; keratinocytes…
Stimulates proliferation of hepatocytes and many other epithelial cells
Transformation growth factor alpha (TGF-a)
Enhances proliferation of hepatocytes and other epithelial cells; increases cell motility
Produced by fibroblasts and most mesenchymal cells, endothelial cells, non-hepatocyte liver cells
HGF
Produced by mesenchymal cells
Increases vascular permeability
Stimulates proliferation of endothelial cells
Maintenance of normal epithelium (highest expression in epithelial cells adjacent to fenestrated epithelium)
VEGF
Induces fibroblast; endothelial and SMC proliferation and also chemotactic for these cells
PDGF
Produced by macrophages, mast cells, endothelial cells..
Chemotactic and mitogenic for fibroblasts; stimulates angiogenesis and ECM protein synthesis
Fibroblast growth factors (FGFs)
Multiple and often opposing effects depending on tissue “pleiotropic”
Stimulates production of collagen, fibronectin, proteoglycans . Inhibits collagen degradation by decreasing MMP activity and increasing TIMP activity (drives scar formation)
Anti-imflammatory cytokine
TGF-beta
occupies the spaces between stromal cells within connective tissue and between parenchymal epithelium and the underlying supportive vascular and smooth muscle structures in some organs
Interstitial matrix
2 major constituents of basement membrane
Type 4 collagen
Laminin
Collagen types I, II, III and V that form linear fibrils stabilised by interchain hydrogen bonding
Fibrillar collagens
Enzyme responsible for cross-linking of fibrillar collagens and providing tensile strength.
Dependent on vitamin C
lysyl hydroxylase
Collagen that contributes to structures of planar BM; help regular collagen-collagen interactions; provide anchoring fibrils that maintain structure of stratified squamous epithelium
Nonfibrillar collagens
confers the ability of tissues to elastically recoil and return to a baseline structure after physical stress
Elastin
Form highly hydrated compressible gels that confer resistance to compressible forces
Consist of long polysaccharides called glycosaminoglycans (e.g keratan sulfate and chondroitin sulfate)
Proteoglycans
Function to enforce the cell cycle checkpoints
CDK inhibitors
stem cells that give rise to the full range of differentiated tissues
totipotent stem cells
stem cells that only have the capacity to replace damaged cells and maintain cell populations within the tissues where they reside
adult stem cells
2 types of cell division used by stem cells for self renewal
- asymmetric division (cell replication in which one daughter cells enters differentiation pathway while the other remains undifferentiated)
- symmetric division (both daughter cells retain self renewal capacity)
2 main types of stem cells
- Embryonic stem cells (totipotent)
- Tissue stem cells (adult stem cells)
Cell cycle phases? (starting with G0 and G1)
G0, G1, S, G2, M
When does the restriction point occur in the cell cycle?
End of G1
2 checkpoints of the cell cycle?
G1/S
G2/M
Tissues where cells may cycle continuously
Labile tissues e.g epidermis and GI tract
Cells that are quiescent but can enter the cell cycle
Stable cells e.g. Hepatocytes
Cells that do have the capacity to proliferate
Permanent cells e.g. neurons and cardiac myocytes
Cells that have the dual property of being able to self renew and give rise to differentiated cells and tissues
Stem cells
Result from introduction of selected genes into differentiated stem cells which reprogram somatic cells to achieve the “stem-ness” of ES cells
Induced pluripotent stem cells
2 key growth factors involved in the second phase of liver regeneration
Hepatocyte growth factors (HGF)
TGF-alpha
(these are produced by many cell types and act on hepatocytes to stimulate cell metabolism and entry of the cells into the cell cycle)
EGFR1 mutations and/or amplification frequently occur in a number of cancers including..
lung
head and neck
breast
brain
These 2 growth factors are produced by macrophages and epithelial cells, are mitogenic for hepatocytes, fibroblasts and a host of epithelial cell types
Epidermal growth factor (EGF)
Transforming growth factor alpha (TGF-alpha)
Receptor for this growth factor is MET which has intrinsic tyrosine kinase activity
MET is frequently overexpressed or mutated in tumours, particularly renal and thyroid papillary carcinomas
HGF
Major angiogenic factor after injury and in tumours
VEGF
Most important inducer of VEGF production
Hypoxia
Antibodies against this growth factor are approved the treatment of tumours such as renal and colon cancers
VEGF
Increased levels of soluble forms of this growth factor receptor in pregnant women may cause preeclampsia
VEGFR-1 (also known as s-FLT-1)
This growth factor may interact with CD20 affecting Rituxumab therapy
Fibroblast Growth Factor (FGF)
Pleiotropic GF with a key role in neoplasia, chronic inflammation and keloids
TGF-beta
What is steatosis?
Abnormal accumulations of triglycerides within parenchymal cells
Pathological processes involving accumulation of cholesterol or cholesterol esters (name 4)
- Atherosclerosis
- Xanthomas
- Cholesterolosis (focal accumulations of cholesterol-laden macrophages in the lamina propria of the gallbladder)
- Niemann-Pick disease Type C
What is Niemann-Pick disease type C?
Lysosomal storage diseases caused by mutations affecting an enzyme involved in cholesterol trafficking, resulting in cholesterol accumulation in many organs
Intracellular accumulations of these usually appear as rounded, eosinophilic droplets, vacuoles, or aggregates in the cytoplasm
Protein
Excessive production of immunoglobulins by plasma cells can cause the ER to become hugely distended with large homogenous eosinophilic inclusions called…
Russell bodies
alpha1-antitrypsin deficiency involves defective transport and secretion of critical…
proteins
Eosinophilic cytoplasmc inclusion in liver cells that is characteristic of alcoholic liver disease and is composed predominantly of keratin intermediate filaments
Alcoholic hyaline
What is meant by the term Hyaline
Alteration within cells or in the extracellular space that gives a homogenous glassy, pink appearance in routine histologic sections stained with H&E
In this disease, glycogen is found in renal tubular epithelial cells, as well as within liver cells, B cells of the islet of Langerhan in the pancreas, and heart muscle cells
Diabetes mellitus
Excessive intracellular deposits of glycogen are seen in patients with an abnormality in either…
glucose or glycogen metabolism
The most common exogenous pigment
Carbon
Accumulation of this pigment blackens the tissues of the lungs (anthracosis) and the involved lymph nodes
Carbon
What is a lipofuscin
An insoluble pigment composed of polymers of lipids and phospholipids in complex with protein.
Not injurious to the cell or functions
Sign of free radical injury and lipid peroxidation
Endogenous pigment seen in cells undergoing slow, regressive changes. Seen in the liver and heart of ageing patients or those with severe malnutrition and cancer cachexia
Lipofuscin
Enzyme involved in formation of melanin
Tyrosinase
Haemoglobin derived, golden yellow to brown, granular or crystalline pigment; one of the major storage forms of iron
Haemosiderin
What are the 2 types of stem cells and the difference between them?
- Embryonic stem cells: present in the inner cell mass of the blastocyst. Totipotent (can give rise to every cell in the body)
- Tissue stem cells (adult stem cells): found in intimate association with the differentiated cells of a given tissue. Normally protected within specialised tissue microenvironments called stem cell niches. Limited lineage potential.
Where are stem cell niches located?
- Bone marrow
- Intestines
- Bulge region of hair follicles
- Limbus of the cornea
- Subventricular zone in the brain
What type of stem cells are found in the bone marrow?
- Haematopoeitic stem cells
- Mesenchymal stem cells (can differentiate into a variety of stromal cells including chondrocytes, osteocytes, adipocytes, myocytes)
Which organs are tissue stem cells (Adult stem cells) located in?
- Bone marrow
- Liver
- Brain
- Skin
- Intestine
What is the role of stem cells in the repair of damaged tissues?
Regeneration. In tissues such as the skin and intestines, tissue stem cells and their progenitors contribute to the restoration of damaged tissues
What is expressed by stem cells and germ cells that makes them resistant to mitotic crisis, and also to avoid the genetic alterations that trigger senescence?
Telomerase
What are the 2 types of cell division of stem cells?
- Symmetric - both daughter cells remain stem cells (occurs in embyrogenesis or during times of stress)
- Asymmetric - only one daughter remains a stem cell; the non-stem cell daughter proceeds along some differentiation pathway
List five non-coding components of the genome.
- Promoter/enhancer regions
- binding sites for factors that organise higher order chromatin structures
- non-coding regulatory RNA (miRNAs, lncRNAs)
- Mobile genetic elements (eg. transposons)
- specialised structure regions e.g. centromeres
What is epigenetics?
Heritable changes in gene expression that are not caused by variations in DNA sequence
Difference between heterochromatin and euchromatin?
Heterochromatin: cytochemically dense and transcriptionally inactive
Euchromatin: disperse and transcriptionally active
What is a histone?
Protein that DNA wraps around
What is the usual effect of histone acetylation, what is the enzyme involved and how is it reversed?
- Histone acetyltransferases (HATs)
- tend to open the chromatin and increased transcription
- can be reversed by histone deacetylases (HDACs)
What is the role of miRNAs?
Modulate translation of target messenger RNAs
Post-transcriptional gene silencing
What is the complex that miRNAs associate with to perform post-transcriptional gene silencing?
RISC (RNA-induced silencing complex)
Roles of proteoglycans in addition to providing compressibility to tissues
- reservoir for growth factors secreted into the ECM
- some are integral cell membrane proteins that have roles in cell proliferation, migration and adhesion (e.g. by binding and concentrating growth factors and chemokines)
Large disulfide linked heterodimer that exists in tissue and plasma forms
Provides the scaffolding for subsequent ECM deposition, angiogenesis and re-epithelialisation in wound healing
Fibronectin
Most abundant glycoprotein in basement membrane.
Connects to underlying ECM components such as type IV collagen and heparan sulfate
Laminin
Family of transmembrane heterodimeric glycoproteins composed of alpha and beta subunits. Provide focal attachment to underlying substrates.
Binding elements can also trigger signaling cascades that regulate cell locomotion, proliferation, shape and differentiation
Integrins
Protein ligands that bind to a distinct family of GPCRs - Frizzled family receptors. Regulars intracellular levels of Beta- catenin
Wnt
What is the difference between a cadherin and integrin?
cadherin is a cell adhesion molecule that is mainly important in cell to cell adhesion, while integrin is a cell adhesion molecule that is mainly important in cell to extracellular matrix adhesion
What is the sarcoplasmic reticulum?
Specialised smooth endoplasmic reticulum in muscle that is responsible for the cyclic release and sequestration of calcium ions that regular muscle contraction and relaxation, respectively
What is the role of ubiquitin in proteasomes?
Covalent binding of ubiquitin identifies proteins for destruction by proteasomes
Which growth factor may be involved in pathogenesis of pre-eclampsia?
VEGF
