1 / 22

Autophagy In Life and Disease

Autophagy In Life and Disease . By: LaShanale Wallace. Overview . Introduction: What is Autophagy? Objective Specific examples Conclusion. What is autophagy…. A vital cellular process by which intracellular components are degraded within the lysosome

newton
Download Presentation

Autophagy In Life and Disease

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Autophagy In Life and Disease By: LaShanale Wallace

  2. Overview • Introduction: What is Autophagy? • Objective • Specific examples • Conclusion

  3. What is autophagy… • A vital cellular process by which intracellular components are degraded within the lysosome • An essential for survival, differentiation, development, and homeostasis

  4. Primary fuNCTION • Is to ensure cell survival through unfavorable situations ex…. • Nutrient absence • Growth factor withdraw • Abundant amount of toxic proteins • Defected organells

  5. Objective • The Roles of Autophagy in life and disease

  6. Autophagy in Life and disease

  7. Literature Review • Focusing on the dual roles of autophagy • Specific examples are… • Its role as cytoprotective autophagy • Its role in skeletal muscle and aging • And its role in pancreatic cancer

  8. Autophagic degradation of active caspase-8: a CROSS TALK MECHANISM BETWEEN AUTOPHAGY AND APOPTOSIS • Purpose • Investigate expression pattern and sublocalization of caspase 8 in TRAIL mediated autophagy • Expression of caspase 8 in shift from autophagy to apoptosis • Materials • HCT colon carcinoma cells treated with TRAIL

  9. Method Quantitative image cytometry, Confocal microscopy assay. Immunoblot Inhibition of autophagy induces caspase 8 activity Cleaved caspase 8 localizes to autophagosome, inhibiting apoptosis Results

  10. Conclusion • This study provides evidence for regulation of caspase 8 activity through autophagy • Capase 8 provides a cross talk mechanism between autophagy and apoptosis

  11. Skeletal muscle autophagy and apoptosis during aging: Effects of calorie restriction and life long exercise • Purpose • Does autophagy in skeletal muscle change with age? • Does exercise and calorie restriction have an effect on autophagy? • Materials • Male Fisher Rats • Ad libthium diet • Four groups: Y,O, OCR, and OCREX • Fast twitch muscle tissue

  12. Results Autophagy decreases with age. Calorie restriction increased autophagy response Exercise had no significant effect Methods and Results

  13. Conclusion • Age is associated with lower levels of autophagy. This leads to increased cellular damage and apoptosis causing muscle loss. • Mild calorie restricted diets increased autophagy in older rats, protecting muscle from cell damage and death

  14. Pancreatic cancers require autophagy for tumor growth • Purpose • Demonstrate that pancreatic cancers are dependent on autophagy for growth • Pancreatic tumor cells are sensitive to autophagy inhibition

  15. Materials meTHODS • Pancreatic ductal adenocarcinoma cells(PDAC) • Control cell lines MCF7, H460, AND HPDE • GFP-LC3 assay • Chloroquine inhibitor • Assay determined degree of autophagy • Immunochemistry monitored LC3 expression during tumor progression • CQ Treatment

  16. Results • PDAC has high levels of basal autophagy • Autophagy is upregulated during tumor progression • PDAC is sensitive to CQ treatment • PDAC Mice treated with CQ live longer

  17. CONCLUSION • Since PDAC is dependent on autophagy, this provides a potential target for therapeutic intervention • Since chloroquine is already used as a anti-malaria therapeutic, clinical trials using drugs targeting autophagy inhibition are strongly suggested for pancreatic cancer

  18. Overall SUMMARY • Functions of autophagy can be beneficial are harmful • Its role to promote cell survival…. • Is beneficial in life processes such as aging • Harmful in diseases like pancreatic cancer • With knowledge researchers can create therapeutics and either inhibit or increase autophagy pathways for more favorable outcomes.

  19. Acknowledgements • Dr. Muganda • MARC Program • Dr. White • Mrs. Petty • Mrs. Sindy Martin

  20. References • Wohlgemuth, S. E., Seo, A. Y., Marzetti, E., Lees, H. A., and Leeuwenburgh, C. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Experimental Gerontology 2010; 45: 138-148. • Young M, T. Y., Khan O, Park S, Hori T, Yun J, Amin S, Hu C, Zhang J, Kester M, and Wang H. Autophagosomal membrane serves as a platform for an intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. The Journal of Biological Chemistry. 2012; 287: 12455-12468. • Rosenfeldt MT, Ryan KM. The multiple roles of autophagy in cancer. Carcinogenesis. 2011; 32(7): 955-963. • http://tp-apg.genes.nig.ac.jp/autophagy/ • http://www.wormbook.org/chapters/www_autophagy/autophagy.html • http://www.invitrogen.com/site/us/en/home/References/Molecular-Probes-The-Handbook/Assays-for-Cell-Viability-Proliferation-and-Function/Assays-for-Apoptosis.html#head7 • http://beaker.sanfordburnham.org/2011/09/autophagy-101/

  21. Questions??????????

More Related