PCL481H1 Lecture 2: PCL481 P2
26 Feb 2017
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Regulation of Intracellular Ca2+ levels
• This process requires energy to maintain the calcium gradient
• A significant portion of energy is used to maintain the calcium balance
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Inappropriate/ Failed repair or Adaptation
• Repair of proteins oxidized at thiol groups:
o Lack of repair will cause SH groups (sensitive) to be oxidized
o Can be repaired but if not- loss of function may occur
• Repair of damaged lipids: repair of oxidative damage→ cells membrane will be disrupted if not repaired
• Repair of damaged DNA
• Degradation and recycling of cell proteins and organelles by autophagy- very regulated process
o Cell recognizes damage, a specific set of processes exists to fix that damage
o Replacement of individual organelles can occur
o If too much damage occurs→ cell death
• Regeneration of damaged axons: neuronal outgrowth or regeneration of nerve cells
• Regeneration of tissues
o i.e. Liver: If this process is fucked then you’re fucked
▪ Transplant is the only thing that can cure it
▪ This most specific to mammals and humans, you cannot live without a liver.
• Active deletion of damaged cells→ Apoptosis
Lecture 1B
Cell Culture Models for Toxicity Testing
Provides a very controlled environment for cellular change. Downside= ignoring very important component of
communication between cells in a 3D space
1. Primary cultured cells: gene expression profiles are very similar to those in the intact organ
a. Short life span, hours to days
2. Finite or immortalized cell lines: Cancer cell lines
a. May have altered gene expression compared to in living tissue
b. Lost ability to senescence
c. Downside= phenotypically not quite the same as the original tissue from which they were derived
3. Genetically engineered cell lines
a. Cancer line where you can artificially insert genes that code a protein of interest such as drug
metabolizing enzyme→ wont have normal toxicity in the presence of these proteins
b. Can introduce bio-activating enzymes or cellular stress reporter genes
4. Stem cells: Pluripotent, derived from embryos that develop into any cell type
a. Can be programmed to differentiate into a specific cell type, i.e. Hepatocytes
Three-Dimensional Culture and cAMP signaling promote the maturation of human pluripotent stem cell-
derived hepatocytes
• Using cAMP to differentiate stem cells (when grown in 3D clusters of cells normally found in tissue)
• cAMP can cause differentiation into liver cells
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