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Mechanisms of Disease I > Robbins - Chapter 1 > Flashcards

Robbins - Chapter 1 Flashcards

1
Q

Differentiate between Single-Nucleotide Polymorphisms and Copy Number Variants.

A

Both are Genetic Variations associated with diseases that are located in NON-PROTEIN-CODING regions of the genome associated with disease.

SNP –> Single Base change (Biallelic); 1% is involved in gene coding sequences

CNV –> 1,000s of Base changes (Biallelic); 50% are involved in gene coding sequences; Could be the reason why humans have different PHENOTYPES!

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2
Q

Differentiate between Heterochromatin and Euchromatin.

A

Heterochromatin –> DENSE and INACTIVE to transcription

Euchromatin –> UNWOUND and ACTIVE to transcription

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3
Q

Which amino acids are involved in the following processes and what is the function of them:

  1. Histone Methylation
  2. Histone Acetylation
  3. Histone Phosphorylation
  4. DNA methylation
  5. Chromatin Organizing Factors
A
  1. Histone Methylation –> Lysine or Arginine; Can activate OR repress transcription
  2. Histone Acetylation –> Lysine; Histone Acetyl Transferases (HATs) will OPEN UP the chromatin and ACTIVATE transcription
  3. Histone Phosphorylation –> Serine; Can activate OR repress transcription
  4. DNA Methylation –> (On Base-Pairs); Results in Transcriptional Silencing
  5. Chromatin Organizing Factors –> (Bind to non-coding regions); Control SPACING between gene enhancers and promoters that control gene expression
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4
Q

Describe the Histone Organization.

A

Nucleosomes –> Octamers of Histone proteins (2x - H2A, H2B, H3, and H4); 1.8 loops of 147 base pairs of DNA

H1 –> LINKER Histone (20-80 nucleotide pairs)

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5
Q

What is non-coding RNA?

A

Genes that are transcribed BUT NOT translated

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6
Q

Describe the function of Micro-RNA (mi-RNA).

A

Posttranscriptional SILENCING of gene expression by mi-RNA is well-conserved mechanism of gene regulation.

22 Nucleotides long on average

Steps: (Figure 1-3, Pg. 5)

  1. Pre-miRNA is transcribed by a mi-RNA gene
  2. Pre-miRNA is exported out of the nucleus into the cytoplasm where it meets up with DICER
  3. DICER is going to cleave the pre-miRNA to make it ACTIVE
  4. Mi-RNA is going unwind and meet up with RISC complex
  5. RISC complex with bound mi-RNA are going to bind to TARGET mRNA and have TWO OUTCOMES:
    • -> IMPERFECT MATCH: RISC is going to tell the RIBOSOME to GTFO and translation will be REPRESSED
    • -> PERFECT MATCH: RISC is going to CLEAVE the target mRNA
  6. End result is GENE SILENCING
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7
Q

Describe the function of Small Interfering RNAs (siRNAs).

A

Short RNA sequences that can be introduced EXPERIMENTALLY into cells and will serve as substrates for DICER (analogous to miRNAs)

Used to “KNOCK-OUT” certain gene products in search for possible therapeutic agents

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8
Q

Describe the function of Long Noncoding RNA (lncRNA).

A

Gene Modification on a Larger Scale (>200 Nucleotides in length)

ROLES of lncRNA (Figure 1-4; Pg. 6)

  1. Promote Gene Activation
  2. Prevent Gene Transcription
  3. Promote Chromatin Modification
  4. Function as SCAFFOLDING to stabilize secondary or tertiary structures and/or multi-subunit complexes that influence chromatin architecture
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9
Q

How does the cell take care of all the “housekeeping” functions that are required for survival?

A

It will compartmentalized various functions in the ORGANELLES!

*** Compartmentalization is going to be able to produce UNIQUE intracellular environments within the cell

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10
Q

Where are proteins synthesized if their destination is the Plasma Membrane? What about the Cytosol?

A

Plasma Membrane –> Rough Endoplasmic Reticulum

Cytosol –> Free Ribosomes

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11
Q

What are the various functions of the cytoskeleton in the cell?

A
  1. Cellular Movement

2. Cellular Shape

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12
Q

Give the general function of the various parts of the cell:

  1. Cytosol
  2. Mitochondria
  3. Rough ER
  4. Smooth ER, Golgi
  5. Nucleus
  6. Endosomes
  7. Lysosomes
  8. Peroxisomes
A
  1. Cytosol –> Metabolism, transport, protein translation (free ribosomes)
  2. Mitochondria –> Energy generation, apoptosis (cytochrome C)
  3. Rough ER –> Synthesis of membrane and secreted proteins
  4. Smooth ER, Golgi –> Protein Modification, sorting, catabolism
  5. Nucleus –> Cell regulation, proliferation, DNA transcription
  6. Endosomes –> Intracellular transport and export, ingestion of extracellular substances
  7. Lysosomes –> Cellular Catabolism
  8. Peroxisomes –> Very long-chain fatty acid metabolism
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13
Q

Which leaflet of the Plasma membrane are the following structures found and what is their function:

  1. Phosphatidylinositol
  2. Phosphatidylserine
  3. Phosphatyidylcholine
  4. Phosphatidylethanolamine
  5. Glycoproteins/Sphingomyelin
  6. Lipid Raft
  7. Cholesterol
A
  1. Phosphatidylinositol –> Both Inner and Outer Membrane Leaflet; Can be hydrolyzed by phospholipase C to make intracellular SECOND messengers (i.e. DAG and IP3)
  2. Phosphatidylserine –> Normally Inner Membrane Leaflet (Can flip to Outer Membrane Leaflet); On the Inner Leaflet it will serve as a NEGATIVE charge for protein interactions; On the Outer Leaflet it will tell PHAGOCYTES to “eat me” because it is undergoing APOPTOSIS; Associated with Platelets
  3. Phosphatidylcholine –> Outer Membrane Leaflet
  4. Phosphatidylehtanolamine –> Inner Membrane Leaflet
  5. Glycoproteins/Sphingomyelin –> Outer Membrane Leaflet; Glycoproteins are important in cell-to-cell and cell-to-membrane interactions
  6. Lipid Raft –> Both Inner and Outer Membrane Leaflets
  7. Cholesterol –> Both Inner and Outer Membrane Leaflets

(Figure 1-6; Pg. 8)

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14
Q

Explain the Four different ways that proteins can associate with the Phospholipid Membrane.

A
  1. Integral or Transmembrane Proteins –> Span the entire membrane with alpha-helices; Typically have POSITIVELY charged Cytosolic domains that are going to associate with negatively charged Proteins
  2. Posttranslational Attachments –> Attached to PRENYL groups (FARNESYL attaches to cholesterol) or FATTY ACIDS (Palmitic or Myristic Acid) that insert on the CYTOSOLIC side of the membrane
  3. Insertion into the Membrane via the GPI-anchors
  4. Peripheral Membrane Proteins –> NONCOVALENT associations with the transmembrane proteins
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15
Q

When plasma proteins function together as large complexes, who is in control of their actions?

A
  1. Chaperone Molecules in the RER

2. Lateral Diffusion in the Plasma membrane followed by complex formation in situ

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16
Q

How can you localize a certain protein to a particular part of the Plasma Membrane?

A
  1. Tight Junctions
  2. Lipid Rafts
  3. Interactions of Proteins with cytoskeletal molecules or Extracellular Matrix
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17
Q

Which Molecules are going to be able to span the membrane via:

  1. Passive Diffusion
  2. Channel Proteins
  3. Carrier Proteins
  4. Caveolae-Mediated Endocytosis
  5. Receptor-Mediated Endocytosis
  6. Exocytosis
  7. Phagocytosis
  8. Transcytosis
A
  1. Passive Diffusion –> Small, nonpolar molecules like O2 and CO2, Hydrophobic molecules, Small Polar Molecules (<75 Daltons)(Water, ethanol, urea); AQUAPORINS are used when you need to transport A LOT of water; IMPERMEABLE to IONS NO MATTER how small they are!!!
  2. Channel Proteins –> Create hydrophilic pores for RAPID transport (usually restricted by size and charge)
  3. Carrier Proteins –> Have a conformational change (relatively slow)
  4. Caveolae-Mediated Endocytosis –> Small Molecules (i.e. Vitamins); noncoated plasma membrane invaginations associated with GPI-linked molecules, cAMP, SRC-family kinases and folate receptor; POTOCYTOSIS (“Cellular Sipping”)
  5. Receptor-Mediated Endocytosis –> Larger Molecules; PINOCYTOSIS (“Cell Drinking”); Involved Plasma Membrane invaginations into a CLATHRIN-COATED vesicle; This is the pathway by which LDL is taken up by the cell
  6. Exocytosis –> Large Molecules are exported from cells
  7. Phagocytosis –> Large non-Clathrin-mediated membrane invagination of large particles (typically in specialized cells i.e marcrophages or neurtrophils)
  8. Transcytosis –> Movement of Large amounts of Solute between the APICAL and BASOLATERAL compartments of the cell
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18
Q

What is an example of a solute that is transported against its concentration gradient in a Carrier Protein?

A

Multidrug Resistance (MDR) Protein –> Pumps Polar Compounds (drugs) out of cells and may render cancer cells resistant to treatment!

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19
Q

Where will water move in a Hypertonic versus a Hypotonic environment (in relation to extracellular Na+)?

A

Hypertonic –> Water moves OUT

Hypotonic –> Water move IN

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20
Q

Describe the function and properties of Actin Filaments.

A

G-actin will noncovalently polymerize to the form F-actin

New G-actin is added or lost at the POSITIVE end of the strand

In Muscle Cells –> Myosin will bind to Actin and moves along it base on ATP hydrolysis

In Non-Muscle Cells –> Controls Cell Shape and Movement

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21
Q

Describe the function and properties of Intermediate Filaments.

A

Large heterogeneous family

Function to instill TENSILE strength in the cells

  1. Lamina A, B, and C –> Nuclear Lamina or all cells (Muscular Dystrophy)
  2. Vimentin –> Mesenchymal Cells (Fibroblasts, endothelium)
  3. Desmin –> Muscle cells, forming the scaffold on which actin and myosin contract
  4. Neurofilaments –> Axons of neurons, imparting stretch and rigidity
  5. Glial Fibrillary Acidic Protein –> Glial cells around neurons
  6. Cytokeratins –> Type I (Acidic or Neutral) and Type II (Basic); Can be used as cell markers because they are different in each cell
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22
Q

Describe the function and properties of Microtubules.

A

Composed of non-covalently polymerized diners of alpha and beta-tubulin

”-“ end –> Embedded in the centrosome near the nucleus

”+” end –> Elongates or reduces in response to various stimuli

KINESINS –> Anterograde Transport (- to +)
DYNEINS –> Retrograde Transport (+ to -)

Involved in CILIA and FLAGELLA

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23
Q

Differentiate between the following Cell-Cell interactions:

  1. Occluding Junctions
  2. Anchoring Junctions
  3. Gap Junctions
A
  1. Occluding Junctions –> “Tight Junctions” will restrict PARACELLULAR movement; Include occludin, claudin, zonulin, and catenin; Helps maintain cellular polarity (located on the APICAL side of the cell)
  2. Anchoring Junctions –> “Desmosomes” mechanically attach cells to each other; SPOT DESMOSOMES or MACULA ADHERENS are used to attach two small spots together (use Desmogleins and Desmocollins); HEMIDESMOSOME attaches the cell to the Extracellular Matrix (use Integrins); BELT DESMOSOMES attach cells together via broad bands (use E-Cadherins)
  3. Gap Junctions –> 6 connexons will make a CONNEXIN and 2 connexins will make a GAP JUNCTION; Permit the passage of ions, nucleotides, sugars, amino acids, vitamins and other small molecules; Permiability of the Gap Junctions is changed by: pH or the Intracellular CALCIUM levels
24
Q

How does the mRNA transcript know that it needs to go to the RER to be translated versus a free ribosome?

A

SIGNAL SEQUENCES on the N-TERMINUS

Present –> RER

Not Present –> Free Ribosome

25
Q

Describe what happens with the CFTR protein in cystic fibrosis.

A

Absence of a single amino acid (phe508), which leads to misfolding, ER retention, and degradation of the CFTR protein

26
Q

What happens to the ER when you have too many misfolded proteins?

A

Leads to the ER stress response (Unfolded Protein Response or “UPR”) that triggers cell death through APOPTOSIS

27
Q

Describe the structure and function of the Golgi Apparatus.

A

Cis –> Trans

Important in transport and modification of proteins

Cis Side –> Can send proteins back to the RER to be recycled

Trans Side –> Can send proteins and lipids to other organelles OR out into the Extracellular Environment

*** Extra prominent in cells specialized for secretion (i.e. Goblet Cells, Bronchial Epithelium or Plasma Cells - Abs production)

28
Q

Where is the Smooth ER more present and why?

A

Gonads or Adrenals –> Synthesize Steroid Hormones

Liver –> Catabolize Lipid-Soluble Molecules

Muscle Cells –> Specialized SER is the Sacroplasmic Reticulum and it is going to be responsible for release and sequestering of CACLIUM ions that regulates muscle contraction and relaxation

*** SER is responsible for sequestering intracellular Ca2+

29
Q

Differentiate between the Autophagy and Heterophagy pathways within Lysosome disposal of cellular waste.

How do Lysosome enzymes get to the Lysosome?

A

Lysosome enzymes are initially tagged with Mannose-6-Phosphate in the Cis end of the Golgi apparatus. If it binds to a M-6-P receptor on the Trans end of the Golgi apparatus, it will be SHIPPED OFF to the Lysosome

HETEROPHAGY –> Lysosomes will fuse with endosomes or phagosomes. End-products may be released into the CYTOSOL for nutrition or into the Extracellular Environment as waste products

AUTOPHAGY –> Organelles or Denatured Proteins are targeted for the lysosome by encircling them with a double membrane derived from the endoplasmic reticulum and marked by LC3 proteins. CELL STRESSORS (i.e. Nutrient depletion or certain intracellular infections) can ACTIVATE the autophagocytic pathway.

(Figure 1-9; Pg. 13)

30
Q

Describe the process of ridding the cell of Denatured/Misfolded Proteins.

A

PROTEASOME

  1. Proteins destined for turnover are tagged with Ubiquitin via the activity of E1, E2, and E3 Ubiquitin Ligases
  2. This will mark the protein for degradation via the Proteasome
  3. Proteasome will degrade the proteins into 6-12 amino acid fragments and they will be able to be recycled

ROUGH ER

  1. High levels of misfolded proteins within the ER will trigger a protective UNFOLDED PROTEIN RESPONSE (Decreases protein synthesis but brings in MORE CHAPERONE proteins to help with refolding)
  2. If this is inadequate to cope with the levels of misfolded proteins, APOPTOSIS is induced

(Figure 1-9; Pg. 13)

31
Q

How are mitochondria similar to bacteria?

Where do Mitochondria come from? Mom or Dad?

What type of disorders are going to present with the mitochondria?

A
  1. Initiate protein synthesis with N-formylmethionine
  2. Sensitive to antibacterial antibiotics

Maternally inherited

Disorders –> X-linked, Autosomal, or Maternally Inherited

32
Q

Describe the various roles of the mitochondria.

A
  1. Energy Generation –> Intermembrane space is the site of ATP synthesis (between the Inner and Outer membranes); H+ travel down their concentration gradient (Core Matrix –> Intermembrane Space) to create ATP; Outer membrane is permeable to small molecules (<500 Daltons); Can produce heat if coupled to THREMOGENIN (inner membrane protein); Half-Life is between 1-10 DAYS
  2. Intermediate Metabolism –> WARBURG EFFECT is when you up-regulate the GLUCOSE and GLUTAMINE uptake in the cell while LOWERING the ATP production; This will refocus the attention on making lipids, nucleic acids and proteins for CELLULAR GROWTH instead of CELLULAR MAINTENANCE
  3. Cell Death –> NECROSIS (will have damage to the outer membrane of the mitochondria which will cause the H+ gradient to be abolished and DECREASE in ATP production) or APOPTOSIS (Cytochorome C will leak out of the mitochondria and bind to an apoptosome which will activate caspases)

(Figure 1-10; Pg. 15)

33
Q

List and describe the various types of Cell-Cell signaling Pathways:

  1. Paracrine Signaling
  2. Autocrine Signaling
  3. Synaptic Signaling
  4. Endocrine Signaling
A
  1. Paracrine Signaling –> Communication with cells in the immediate vicinity (minimal diffusion, signal is rapidly degraded, taken up by other cells or trapped in the ECM)
  2. Autocrine Signaling –> Molecules secreted by a cell will affect the SAME cell
  3. Synaptic Signaling –> Activated neurons secrete neurotransmitters at specialized cell junctions (synapses) onto target cells
  4. Endocrine Signaling –> Release into the bloodstream and acts on target cells at a distance
34
Q

Differentiate between Intracellular and Cell-surface Receptors.

A

INTRACELLULAR Receptors –> Transcription factors that are activated by Lipid-Soluble ligands that can easily cross the plasma membrane (uncommonly, NO is going to DIRECTLY activate Guanylyl Cyclase to generate cGMP)

CELL-SURFACE Receptors –> Generally transmembrane proteins with extracellular domains that bind soluble secreted ligands; Depending on the receptor, ligand binding can then (1) open ion channels, (2) Activate an associated GTP-binding regulatory protein, (3) Activate an endogenous or associated enzyme often a tyrosine kinase, or (4) Trigger a proteolytic event or a latent transcription factor. (2) and (3) are associated with growth factor signaling pathways that drive cell proliferation

35
Q

Describe the various receptors that possess an associated Kinase Activity:

  1. Receptor Tyrosine Kinase
  2. Nonreceptor Tyrosine Kinase
A
  1. RECEPTOR TYROSINE KINASE –> Integral Membrane Proteins (i.e. Insulin, epidermal growth factor and platelet derived growth factor); Ligand-Induced cross-linking activates intrinsic tyrosine kinase domains located in their cytoplasmic tails
  2. NONRECEPTOR TYROSINE KINASE –> Receptors that DO NOT have any intrinsic catalytic activity; SRC-Family Kinases contains SH2 (binds to receptors phosphorylated by another kinase) and SH3 (mediates other protein-protein interactions, often involving PROLINE-RICH domains)
36
Q

Describe the various receptors:

  1. G-Protein Coupled Receptors
  2. Nuclear Receptors
  3. Notch Family Receptors
  4. Frizzled Family Receptors
A
  1. G-Protein Coupled Receptors –> Transverse the plasma membrane 7 times; Ligand binding causes GDP to GTP conformation; Downstream effects are activation of cAMP and IP3 (increases intracellular Calcium concentrations from the Endoplasmic Reticulum)
  2. Nuclear Receptors –> Lipid-Soluble ligands can diffuse into cells where they interact with intracellular proteins to form a receptor-ligand complex that directly bind to nuclear DNA (can be activation or repression of gene expression)
  3. Notch Family Receptors –> Ligand binding to Notch will cause cleavage of the cytoplasmic part (Notch) and that will translocate into the nucleus to form a transcriptional complex
  4. Frizzled Family Receptors –> Normally Beta-Catenin is constantly targeted with UBIQUITIN; Wnt binding to Frizzled brings over DISHEVELED that will disrupt the degradation targeting complex! Beta-Catenin will then translocate to the Nucleus where it is going to form a transcriptional complex

(Figure 1-11; Pg. 17)

37
Q

List, in order, the phases of the Cell Cycle.

A

G1 - S - G2 - M - Cell Division

Cells that are “quiescent” and not actively cycling –> G0

38
Q

Describe the various checkpoints of the cell cycle.

Which molecule is responsible for enforcing the checkpoints?

A

G1-S Checkpoint –> Cells with genetic imperfections will not make it through here! Makes sure the DNA is all in order.

G2-M Checkpoint –> Makes sure that the DNA is replicated correctly

CDK INHIBITORS (CDKIs) –> Inhibit cyclin CDK4 and cyclin CDK6 (p15-p16-p18-p19); Inhibit multiple cyclin CDK complexes (p21-p27-p57)

39
Q

Describe which cyclin-CDK complexes are active during each phase of the cell cycle.

A

G1-S –> Cyclin D-CDK4 and Cyclin D-CDK6, Cyclin E-CDK2 (Regulate this checkpoint by PHOSPHORYLATING the Rb Protein)

S Phase –> Cyclin A-CDK2 and Cyclin A-CDK1

G2-M Checkpoint –> Cyclin B-CDK1 is ESSENTIAL to regulate this checkpoint

40
Q

Describe the two important properties of stem cells.

A
  1. Self-Renewal –> Helps them to maintain their numbers

2. Asymmetric Division –> One cell becomes a daughter cell and the other remains undifferentiated

41
Q

Differentiate between:

  1. Embryonic Stem Cells
  2. Tissue Stem Cells (Adult Stem Cells)
  3. Induced Pluripotent Stem Cells
  4. CRISPR-Cas9
A
  1. Embryonic Stem Cells –> Most Undifferentiated, present in the inner cell mass of the blastocyst, TOTIPOTENT
  2. Adult Stem Cells –> Multipotent
  3. Induced Pluripotent Stem Cells –> Take the patient’s cell and inject it with genes for “Stem-ness” for it to undifferentiate.
  4. Nuclease (Cas9) and Guide RNA (CRISPR)
42
Q

Describe the function of adapter proteins.

A

Proteins that function as molecular connectors that physically LINK different enzymes and promote the assembly of complexes (can be Integral membrane proteins or Cytosolic proteins)

43
Q

Describe the outcome of most transduction pathways.

What are some examples of these molecules?

A

Influence cellular function by modulating gene transcription through the activation and nuclear localization of transcription factors

MYC and JUN –> Cell Growth

p53 –> Cell Arrest

44
Q

Where does most of the binding of transcription factors occur?

A

Enhancers –> Long-Range Regulatory elements

45
Q

Describe the function and sources of:

  1. Epidermal Growth Factor (EGF)
  2. Transforming Growth Factor-alpha (TGF-alpha)
A
  1. Epidermal Growth Factor –> Activated Macrophages, Salivary Glands, Keratinocytes and many other cells; Mitogenic (promotes cell division) for keratinocytes and fibroblasts, stimulates keratinocyte migration, and stimulates formation of granulation tissue
  2. Transforming Growth Factor-alpha –> Activated macrophages, keratinocytes, and many other cells; Stimulates proliferation of hepatocytes and many other epithelial cells

*** ERBB2 (aka HER2) is overexpressed in a subset of Breast Cancers

46
Q

Describe the function and sources of Hepatocyte Growth Factor.

A

Hepatocyte Growth Factor –> Fibroblasts, stromal cells in the LIVER, endothelial cells; Enhances proliferation of hepatocytes and other epithelial cells, increases cell motility

*** Receptor is MET and it has an intrinsic tyrosine kinase activity

*** Frequently overexpressed in RENAL and THYROID papillary carcinomas

47
Q

Describe the function and sources of Platelet-Derived Growth Factor.

A

Has 3 isoforms that are ALWAYS active (PDGF- AA, AB, and BB) and PDGF-CC/PDGF-DD must be activated by proteolytic cleavage

Sources –> Platelets, Macrophages, endothelial cells, smooth muscle cells, and keratinocytes

Function –> Chemotactic for neutrophils, macrophages, fibroblasts, and smooth muscle cells; activates and stimulates proliferation of fibroblasts, endothelial, and other cells; stimulates ECM protein synthesis

48
Q

Describe the function and sources of Vascular Endothelial Growth Factor.

A

GROWTH FACTORS

  1. VEGF-A is the major ANGIOGENIC (inducing blood vessel development) factor after injury and in tumors
  2. VEGF-B and PIGF –> Involved in embryonic vessel development
  3. VEGF-C and VEGF-D –> Stimulate BOTH angiogenesis and lymphatic development

*** Also induce Vascular Dilation and Increased Vascular Permeability

***HYPOXIA is the most IMPORTANT inducers of VEGFs through pathways that involved intracellular hypoxia-inducible factor (HIF-1)

RECEPTORS
VEGFR-2 –> Highly expressed in endothelium and is the MOST IMPORTANT for angiogenesis

Anti-VEGF antibodies are used for:

  1. “Wet” age-related Macular Degeneration
  2. Angiogenesis associated with retinopathy or prematurity
  3. Leaky vessels that lead to diabetic macular edema

*** Increased levels of soluble versions of VEGFR-1 (s-FLT-1) in pregnant woman may cause PREECLAMPSIA

49
Q

Describe the source and function of Fibroblast Growth Factor.

A

GROWTH FACTORS

  1. Acidic FGF –> aFGF or FGF-1
  2. Basic FGF –> bFGF or FGF-2 (Has all the properties for angiogenesis also)
  3. FGF-7 –> AKA Keratinocyte Growth Factor

Source –> Macrophages, Mast Cells, Endothelial Cells, and many other cell types

Function –> Chemotactic and mitogenic for FIBROBLASTS, stimulates angiogenesis and ECM protein synthesis, Wound Healing

50
Q

Describe the source and function of Transforming Growth Factor-Beta.

A

Belongs to the same family as BMPs, Activins, Inhibins, and Mullerian Inhibiting Substance

TGF-Beta Receptors are going to have Serine/Threonine Kinase activity; Downstream effects are going to involve Smads (Cytoplasmic TF)

51
Q

List the Key Functions of the Extracellular Matrix.

A
  1. Mechanical Support
  2. Control of Cell Proliferation –> Provides a depot for a variety of LATENT growth factors that can be activated during injury or inflammation
  3. Establishment of tissue microenvironments
52
Q

What are the two basic forms of the Extracellular Matrix?

A
  1. Interstitial Matrix –> Present in spaces between cells in connective tissue and is synthesized by FIBROBLASTS
  2. Basement Membrane –> TYPE IV COLLAGEN and LAMININ are the major components of the basement membrane
53
Q

Describe the structure and the purpose of:

  1. Collagens
  2. Elastin
  3. Proteoglycans and Hyaluronan
  4. Adhesive Glycoproteins and adhesion receptors
A
  1. COLLAGENS –> FIBRILLAR COLLAGENS (Types I, II, III, and V) form linear fibrils that are stabilized by interchain hydrogen bonding (uses LYSYL Oxidase which is dependent on VITAMIN C –> OSTEOGENESIS IMPERFECTA and EHLER-DANLOS SYNDROME); NON-FIBRILLAR COLLAGENS (Type IV) is going to help with the basement membrane
  2. Elastin –> Has the ability to be stretched and return to its original shape; Contains central core of elastin with FIBRILLIN (Deficiencies in fibrillin –> Marfan Syndrome)
  3. Proteoglycans and Hyaluronan –> Form highly hydrated compressible gels that confer resistance to compressive forces; GAGs attach to Core protein which attaches to Hyaluronic Acid via Linker Protein; Also serve as a RESERVOIR for Growth Factors
  4. Adhesive Glycoproteins and Adhesion Receptors –> Contain three main proteins: 1. FIBRONECTIN (Has specific domains that can bind to distinct ECM components; Provides scaffolding in wound healing); 2. Laminin (MOST ABUNDANT glycoprotein in the basement membrane); 3. Integrins (Transmembrane heterodimers)
54
Q

Describe the Warburg Effect.

A

You bring in a bunch of Glucose and Glutamine and shuttles it off to make more Lipids to maintain the cell division (i.e. Plasma Membranes)

Pg. 14

55
Q

Describe all of the growth factors that are involved in Regeneration and repair.

A

Table 1-1; Pg. 19

Mechanisms of Disease I (4 decks)

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