Chapter 3 Flashcards
Hyperplasia
-Increase in the amount of organic tissue that results from cell proliferation
-Some human organs continue to grow and increase in size after development is complete by hyperplasia, mitotic cell growth in which the tissue or organ increases in size by increasing the number of cells within it
Hypertrophy
-Increase in the volume of an organ or tissue due to the enlargement of its component cells
-the expansion of the size of each individual cell rather than by generating new cells to increase the number of cells
-A disadvantage of organs that have attained their final size by hypertrophy is that when these nondividing cells die, they are usually replaced by scar tissue cells rather than by the same type of cells that were lost.
-Whenever normal cells within an organ are replaced with scar tissue, some organ function is reduced. The degree of function lost is proportionate to the amount of scar tissue present.
Figure 3-1
Apoptosis
-Programmed cell death or cellular suicide
-Cell aging in tissues capable of mitosis is determined by the number of preprogrammed cell divisions it can undergo.
- For optimum function, mitosis must be balanced with apoprosis, Normal cell function requires strict genetic regulation over both processes.
cell adhesion molecules (CAMs).
-Normal cells have several different cell surface proteins that allow normal cells of the same type to adhere tightly rogether. These proteins are known as cell adhesion molecules (CAMs).
-Thus, normal cells do not leave their parent organ or tissue.
Characteristics of Normal Cells
Appearance
-Each eype of normal cell has a distinctive or differentiated appearance, including size and shape. The structure and appearance of normal cells reflect their function. Normal cells have a relatively small nuclear-to-cytoplasmic ratio when they are not undergoing mitosis.
Function
-All normal cells perform at least one specific job, called a differentiated function, that helps whole-body function.
Adherence
-Normal cells have several different cell surface proteins that allow normal cells of the same eype to adhere tightly rogether. These proteins are known as cell adhesion molecules (CAMs).
Ploidy
-Normal human somatic cells have a nucleus and are diploid, containing 23 pairs of human chromosomes (or 46 individual chromosomes), a condition known as euploidy. The only normal mature human cells that are not diploid are erythrocytes, which have extruded the nucleus and do not contain any chromosomes, and sex cells (oocytes or eggs and spermatocytes or sperm), which are haploid, containing only half of each pair of chromosomes (23 total chromosomes).
Ploidy
-Normal human somatic cells have a nucleus and are diploid, containing 23 pairs of human chromosomes (or 46 individual chromosomes), a condition known as euploidy.
-The only normal mature human cells that are not diploid are erythrocytes, which have extruded the nucleus and do not contain any chromosomes, and sex cells (oocytes or eggs and spermatocytes or sperm), which are haploid, containing only half of each pair of chromosomes (23 total chromosomes).
Contact inhibition of mitosis.
Density-dependent inhibition of cell growth
-Normal cells that have retained mitotic ability are inhibited from mitosis when their membranes are com- pletely in contact with the membranes of other cells, a condition known as contact inhibition of mitosis.
-The presence of cell surface membranes that are untouched by the membrane of another cell is a signal that mitosis is needed.
-Once a normal cell is completely surrounded by other cells and its membrane is contacted directly on all surface areas with the membranes of other cells, it no longer undergoes mitosis.
-Another term for this characteristic is density-dependent inhibition of cell growth.
- The purpose of this feature is to prevent inappropriate tissue overgrowth.
oncogenes
suppressor genes,
-Normal cell populations are regulated by a balance between products produced by oncogenes, which promote entering and completing the cell cycle, and products produced by suppressor genes, which restrict or inhibit entering and moving through the cell cycle.
-Thus, oncogene products are promitotic and induce cells to enter and complete the cell cycle to divide.
-Suppressor gene products inhibit all aspects of mitosis and also trigger apoptosis.
Controlled Mitosis
-cells not actively reproducing (undergoing mitosis) are outside of the cell cycle in G0, the reproductive resting state, and continue to perform all their usual differentiated functions.
-Cells that retain mitotic ability must exit the G0 state to enter the cell cycle.
-Among all normal cells capable of mitosis, the step of leaving G0 and entering the first phase of the cell cycle, G1 is severely restricted.
-This restriction includes the presence or absence of external and internal signals, many of which are gene products.
-Once a cell enters the cell cycle, it responds only to internal signals.
-Cells in the cycle must either progress through the cycle or be arrested at some point in the cycle. Cells that are arrested are nonfunctional and usually die.
-Some of the checks, known as restrictionpoint controls. that are placed on a cell before it can enter the cell cycle include the following:
• The cell has retained its mitotic ability.
• A need exists for cell division in the specific tissue where the cell resides. Are more cells needed in this
tissue from previous cell damage or loss? Are more cells needed in this tissue because the tissue needs to
increase in size (as in normal development)?
• Adequate nutritional Stores are present (especially protein, glucose, and oxygen) to support existing and
new cells.
• The cell has a sufficient energy supply or can produce enough energy to participate in cell division and synthesize additional membranes, proteins, and organelles.
[controlled mitosis]
Signal transduction
Figure 3-2
-Information on the presence of external events that inform the cell of a need for cell division is sent to the cell’s nucleus through a process known as signal transduction.
-This communication system allows information about events, conditions, and substances external to the cell to reach the nucleus and then influence whether the cell divides, undergoes apoprosis, or performs its differentiated functions.
-Many signal transduction pathways are within cells that have retained mitotic ability.
-Some pathways are promitotic, and others transfer signals to suppress cell division.
-Known factors that are external prorniroric signals include growth factors (such as epidermal growth factor [EGF] and vascular endothelial growth factor [VEGF]); CAMs; steroid hormones; and cell-to-cell contact through direct touching, chemical transmission, and electrical interactions.
-Most of these pathways involve the occupation or activation of membrane receptors.
-Most cells have multiple receptor types and complicated interconnecting signal transduction pathways.
Promitotic signal transduction pathway
-Figure 3-3 presents a single promitotic signal transduction pathway in a cell segment that, when activated because of external conditions, leads to oncogene activation and the promotion of cell division.
-Any of several conditions can initiate activation of this pathway, including growth factors that bind to receptors, the interaction of drugs with the cell plasma membrane, the presence of adhesion proteins, changes in ion movement (especially sodium and calcium), ligand binding, and other cell-to-cell interactions.
When the pathway is activated, one of the first responses is the activation of enzymes that increase the intracellular concentration of a variety of tyrosine kinase (TK) enzymes.
-The end result of the activation of any promitotic signal transduction pathway is increased production of transcription factors.
-Transcription factors are proteins that enter a cell nucleus and regulate transcription for a specific gene or set of genes.
Transcription factors
-proteins that enter a cell nucleus and regulate transcription for a specific gene or set of genes.
Important concepts
• Suppressor gene products control the expression of oncogene products.
• Oncogene products arealwaysprornitoric.
• Control is exerted at every phase of the cell cycle.
• Activation of most of the promitotic gene products requires the addition of a phosphate group to their structures.
• These promitotic products can be deactivated by removing a phosphate group from their structures
[G1 Phase]
Pt. 1
-When external promitotic signals reach the cell’s nucleus and the checkpoint information indicates that the resources are adequate, the cell exits G0 and enters G1, the first phase of the cell cycle.
-Progression to the next phase is determined by the presence of cyclins. Cyclins are a group of promitotic proteins produced by specific oncogenes that, upon activation, propel the cell forward through all phases of the reproduction cycle.
-Normally, the oncogene expression of cyclins is carefully regulated by suppressor gene products. Cyclin activation requires the attachment of a phosphorous molecule to the cyclin structure, a process known as phosphorylation.
-Phosphorylation is performed by a variety of TKs.
-TKs activate many transcription factors at different steps in the signal transduction pathway, and they activate cyclins in the cell cycle. A wide variety of TKs exists, most of which are products of oncogenes. Some are unique to the cell type; others are produced only in cancer cells that express a specific oncogene mutation.
-Cyclins are activated by cyclin-dependent kinases (CDKs).
-The CDKs combine with cyclins to form complexes that start the cellular reproductive processes. In normal cells, cyclins and CDKs are carefully regulated by suppressor genes so that cell division occurs only when it is needed and to the degree it is needed.
[G1 Phase]
Cyclins
-Progression to the next phase is determined by the presence of cyclins. Cyclins are a group of promitotic proteins produced by specific oncogenes that, upon activation, propel the cell forward through all phases of the reproduction cycle.
-Cyclins are activated by cyclin-dependent kinases (CDKs).
-The CDKs combine with cyclins to form complexes that start the cellular reproductive processes. In normal cells, cyclins and CDKs are carefully regulated by suppressor genes so that cell division occurs only when it is needed and to the degree it is needed.
[G1 Phase]
TKs
-TKs activate many transcription factors at different steps in the signal transduction pathway, and they activate cyclins in the cell cycle. A wide variety of TKs exists, most of which are products of oncogenes. Some are unique to the cell type; others are produced only in cancer cells that express a specific oncogene mutation.
[G1 Phase]
Pt 2.
-The type of cyclins present in a cell during mitosis varies by the phase of the cycle.
-Differences in cyclin types determine whether the cell progresses through the phases of the cell cycle and whether the cycle is completed so that two new cells are generated.
-More than 20 different families of cyclins have been identified (A through T).
-The A, B, and D cyclin families are the most well characterized.
-The most common signal for leaving G0 and entering G1 is the formation of the cyclin-D/CDK complex, which is formed by combining cyclin-D with its specific CDK. ]
-Additional complexes of other cyclins and their specific CDKs form to allow progression through each phase of the cell cycle.
-All cyclins and CDKs are made in the cell in response to specific oncogene activation.
-Figure 3-2 shows the activity of various cyclin complexes in the cell cycle.
-Late in G1, additional cyclin/CDK complexes form to move the cell into S phase.
-These complexes promote DNA transcription and protein synthesis.
-The resulting response is a greater expression of promitotic cyclins by oncogenes and a reduced expression of suppressor gene products that inhibit cell division.
-Progression into S phase requires that regulator proteins be phosphorylated to work with transcription factors.
-All of these processes are under genetic control.
-A major regulator of the cell cycle for many types of normal cells is the Tp53 suppressor gene product.
-It is known as the “guardian of the genome,” and its activation restricts the progression of cells from G1 into S phase.
-Anything that damages the Tp53 gene results in less restriction for progression of the reproductive cell cycle.
[S Phase]
-DNA replication is the major activity of S phase.
- The result is two complete sets of DNA.
-The cyclin- E/CDK2 complex drives DNA replication by activating the enzymes needed to produce nucleotides.
-Another complex, the cyclin-A/CDK complex, then permits the synthesis of all substances needed for DNA replication.
-After DNA is replicated, cyclin-B activates other kinases for completion of S phase and progression into the G2 phase.
[G2 Phase]
-This phase of the cell cycle is characterized by intense protein synthesis for proteins that are important in M phase and for those that provide routine cell maintenance.
-The cyclin-B/Cdc2 complex drives these actions and then moves into the nucleus to trigger gene expression for the production of other complexes and proteins of cell structures needed for M phase (e.g., centrioles and spindle fibers).
[M Phase]
-M phase is the part of the cell cycle in which true mitosis, which results in two new daughter cells, occurs.
-During this phase, DNA is organized into chromosomes. As discussed in Chapter I , the subphases of M phase are prophase, prometaphase, metaphase, anaphase, and telophase (seeFig.I-II).
-Microtubular spindle fibers form from the centrioles due to the interaction of cyclins and an activating enzyme called aurora kinase.
-As each chromosome forms, it moves to the center of the cell and attaches each chromatid to one end of a spindle fiber under the influence of aurora kinase and the protein survivin.
- At this point, nucleokinesis occurs, in which each chromosome is pulled apart at the centriole so that the two sets of chromosomes are separated within the single large cell.
-This process is immediately followed by cytokinesis, which is the separation of this cell into two new cells that each have a complete set of chromosomes.
[M Phase]
Nucleokinesis
each chromosome is pulled apart at the centriole so that the two sets of chromosomes are separated within the single large cell.
[M Phase]
Cytokinesis
-Separation of this cell into two new cells that each have a complete set of chromosomes.
Apoptosis
Process pt 1.
-A major signal for normal apoptosis is the shortening of the relorneric DNA at the tips of the cell’s chro- mosomes, which occurs with each round of cell division
-When the cell is healthy, relorneric DNA is maintained by the enzyme telomerase that was produced in the cell during fetal life.
-The cell has achieved its preprogrammed number of cell divisions when telomerase is depleted and the telomeric DNA is completely gone.
-Loss of the telomeres leads to chromosomal unraveling and fragment formation. This response triggers a variery of genetic and intracellular signals for self-destruction.
-A major protein for apoprosis is the product of the Tp53 rumor suppressor gene.
-This gene is expressed when cells reach their preprogrammed age or are damaged.
-The response to this protein is either apoptosis or the arrest of these cells at the G1 or G2 phases of the cell cycle.
-Other substances synthesized and released in
response to the Tp53 gene product include cytochrome c and the p21 protein, both of which are important in apoptosis.
Apoptosis
Process pt 2.
-The sequence of events in which apoptotic signals are received by normal cells starts with endonuclease enzymes degrading the cell’s DNA and mitochondria, thereby releasing cytochrome c.
-This substance activates apoptotic protease activation factor (Apaf-1), which then activates the enzyme caspase 9.
-Activation of caspase 9 starts a cascade reaction to activate the whole family of caspases, resulting in the degradation of the cell’s internal structures and fracturing of the cell membrane.
-The cell breaks into smaller fragments (apoptotic bodies) that are eliminated as debris by white blood cells.
-Thus, the genetically controlled processes of apoptosis balanced with the strict controls of cell growth ensure that organs remain optimally functional.
-When cell division is not needed, external signals (such as growth-factor inhibitors and the surrounding of a cell plasma membrane with other cells) are sent that inhibit the promitotic cell division signal transduction pathways (Fig. 3-4).
-This inhibition leads to low levels of TKs and reduced levels of promitotic transcription factors.
-Suppressor gene activity is increased, resulting in the production of more suppressor gene products that inhibit the synthesis of cyclins and CDKs by oncogenes.
-Many sup-pressor genes exist, and although all are present in every cell type, specific suppressor genes may be more active in selected types of tissues.
-For example, the BRCA1 suppressor gene appears most active in suppressing excessive cell division in breast, ovary, and genitourinary tract tissues.
[EARLY EMBRYONIC CELL BIOLOGY]
anaplastic
“without a specific shape” (morphology).
[EARLY EMBRYONIC CELL BIOLOGY]
pluripotency
A pluripotent cell can, under the right condi-tions, become any cell type in the human body. These are the original “stem” cells.
[EARLY EMBRYONIC CELL BIOLOGY]
Differentiation
process by which a cell leaves the pluripotent stage and acquires the maturational features and functions of a specific cell type
Characteristics of Early Embryonic Cells
2 pics screenshots
Cell Growth
-Early embryonic cells do not display contact inhibition of cell growth, even when all sides of these cells are in continuous contact with the surfaces of other cells.
-These cells perform rapid and continuous cell division, with a minimal amount of time spent in G0.
-They reenter the cell cycle nearly as soon as they leave it and do not respond to signals for apoptosis.
-These cells have long telomeres that do not shorten with each cell division, and they have a relatively large amount of the enzyme telomerase.
-(Later in fetal life, apoptosis is needed for normal development; however, it is not a characteristic of early embryonic cells.)
-The only job for an embryo during the first week after conception is to increase the number of cells within it.
[EARLY EMBRYONIC CELL BIOLOGY]
Commitment
-involves adjusting the activity of the promitotic oncogenes and the genes that regulate dif-ferentiation.
-At about day 8 after conception in humans, early embryonic cells each commit to a differentiation pathway and are no longer pluripotent.
-At this stage, cells have not yet taken on any differentiated features, but they begin to position themselves within the embryo in areas that will eventually become specific organs or tissues.
-So, cells scattered throughout the early embryo that are destined to become heart cells migrate and join together in the area that will eventually become the chest.
-Thus, migration continues on a limited basis after commitment.
[EARLY EMBRYONIC CELL BIOLOGY]
Early Embryo Stage
-Just after conception and for the next 14 days, an unborn baby is known as an early embryo.
-The cells in this early embryo have not yet started to differentiate into specific organs or tissues, and they all have essentially the same appearance (see Fig. 3-6).
-Because the placenta has not yet completely formed, very few drugs affect an unborn baby at this stage unless the mother is harmed. However, toxins and infectious organisms can damage the early embryo and can cause a spontaneous abortion (miscarriage).
-More commonly, though, genetic issues that disrupt commitment and differentiation are responsible for miscarriage at this stage.
