Deadly triplex: smoke, autophagy and apoptosis.
Stefan W Ryter1, Hilaire C Lam, Zhi-Hua Chen
1Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. sryter@partners.org
Autophagy
|January 5, 2011
Summary
Autophagy protein LC3B promotes lung cell death and injury in chronic obstructive pulmonary disease (COPD) models. Inhibiting LC3B may offer a new therapeutic strategy for COPD treatment.
Area of Science:
- Cellular Biology
- Pulmonary Medicine
- Molecular Mechanisms of Disease
Background:
- Autophagy is a cellular degradation process crucial for cell survival.
- The role of autophagy in regulating apoptosis, or programmed cell death, is not fully understood.
- Autophagic markers are elevated in human chronic obstructive pulmonary disease (COPD) lungs and in mouse lungs exposed to cigarette smoke.
Purpose of the Study:
- To investigate the role of the autophagic protein microtubule-associated protein 1 light chain 3B (LC3B) in regulating lung cell death.
- To elucidate the molecular mechanisms by which LC3B influences apoptosis in epithelial cells during chronic cigarette smoke exposure.
- To explore the potential of targeting the autophagic pathway for COPD treatment.
Main Methods:
- Analysis of autophagic and apoptotic markers in human COPD lung tissue and mouse models of chronic cigarette smoke exposure.
- Utilizing LC3B knockout (LC3B(-/-)) and caveolin-1 knockout mice.
- Investigating the interaction between LC3B, Fas, and caveolin-1 in epithelial cells.
Main Results:
- LC3B knockout mice exposed to cigarette smoke exhibited reduced lung apoptosis and airspace enlargement.
- LC3B forms a complex with the death receptor Fas in lipid rafts, dependent on caveolin-1.
- Genetic interference of caveolin-1 increased cigarette smoke-induced apoptosis, while caveolin-1 knockout mice showed heightened autophagic markers, apoptosis, and airspace enlargement.
Conclusions:
- LC3B promotes tissue injury in response to chronic cigarette smoke exposure.
- LC3B regulates apoptosis through interactions with caveolin-1 and Fas in epithelial cells.
- Targeting the autophagic pathway presents a potential therapeutic avenue for COPD.
More Related Videos
06:12LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
Published on: May 3, 2024
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
Related Concept Videos
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
01:18Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...