Cell Death & Renewal (part 2)

Transcription

1 17 Cell Death & Renewal (part 2)

2 Programmed Cell Death A major signaling pathway that promotes cell survival is initiated by the enzyme PI 3-kinase, which phosphorylates PIP2 to form PIP3, which activates the protein-serine/threonine kinase Akt. Akt phosphorylates a number of proteins that regulate apoptosis.

3 Figure The PI 3-kinase pathway and cell survival

4 Figure Cell death receptors Extrinsic pathway Polypeptides in the tumor necrosis factor (TNF) family are the signals. Receptors activate an initiator caspase, caspase-8. Caspase-8 can cleave and activate effector caspases and Bid, which leads to activation of caspase-9.

5 Programmed Cell Death Programmed cell death can also occur by nonapoptotic mechanisms such as autophagy. In normal cells, autophagy is a mechanism for gradual turnover of cell components. In starvation conditions, degradation of components provides energy and recycles materials.

6 Programmed Cell Death Autophagic cell death does not require caspases. Dying cells are characterized by an accumulation of lysosomes. It can be activated by cellular stress and provide an alternative to apoptosis when apoptosis is blocked.

7 Autophagy Yoshinori Ohsumi (1945~) Nobel Prize in Physiology or Medicine (2016) Autophagy, the term was coined in 1963

8 Programmed Cell Death Some forms of necrosis (necroptosis) can be a programmed cell response to stimuli such as infection or DNA damage. Regulated necrosis may provide an alternative pathway of cell death if apoptosis does not occur.

9 Mode of cell death

10 Stem Cells and the Maintenance of Adult Tissues In early development, cells proliferate rapidly, then differentiate to form the specialized cells of tissues and organs. To maintain a constant number of cells in adult tissues, cell death must be balanced by cell proliferation. Most differentiated cells in adult animals are no longer capable of proliferation. If these cells are lost they are replaced by proliferation of cells derived from self-renewing stem cells.

11 Figure Skin fibroblasts Some differentiated cells retain the ability to proliferate as needed, to repair damaged tissue throughout the life of the organism. Fibroblasts in connective tissue can proliferate quickly in response to platelet-derived growth factor (PDGF) released at the site of a wound.

12 Stem Cells and the Maintenance of Adult Tissues Endothelial cells that line blood vessels can proliferate to form new blood vessels for repair and regrowth of damaged tissue. Proliferation is triggered by vascular endothelial growth factor (VEGF), which is produced by cells that lack oxygen.

13 Figure Proliferation of endothelial cells

14 Figure Liver regeneration The epithelial cells of some internal organs are also able to proliferate to replace damaged tissue. Liver cells, normally arrested in the G0 phase of the cell cycle, are stimulated to proliferate if large numbers of liver cells are lost (e.g., by surgical removal).

15 Stem Cells and the Maintenance of Adult Tissues Stem cells are less differentiated, self-renewing cells present in most adult tissues. They retain the capacity to proliferate and replace differentiated cells throughout the lifetime of an animal. The key property of stem cells: They divide to produce one daughter cell that remains a stem cell and one daughter cell that divides and differentiates. Stem cells are self-renewing and serve as a source of differentiated cells throughout life.

16 Figure Stem cell proliferation

17 Stem Cells and the Maintenance of Adult Tissues Many types of cells have short life spans and must be continually replaced by proliferation of stem cells: Blood cells, sperm, epithelial cells of the skin and in the lining of the digestive tract. Hematopoietic (blood-forming) stem cells were the first to be identified. There are several types of blood cells with specialized functions; all are derived from the same population of stem cells.

18 Figure Formation of blood cells

19 Figure Renewal of the intestinal epithelium Epithelial cells that line the intestines live only a few days before they die by apoptosis. New cells are derived from the continuous but slow division of stem cells at the bottom of intestinal crypts. New cells proliferate for three to four cell divisions and then differentiate.

20 Figure Renewal of the intestinal epithelium

21 Figure Stem cells of the skin Skin and hair are also renewed by stem cells. The epidermis, hair follicles, and sebaceous glands are all maintained by their own stem cells.