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Cardiopulmonary response Zn

Cardiopulmonary response Zn. INTRODUCTION (PM, Zn, ENaC) Zn → ENaC↑ → (ASL and MCT)↓ CONCLUSION. Particulate matter (PM), Zn and Pulmonary and Systemic Toxicity. Zn soluble component of PM (ambient, combustion, emissions) critical for cardiopulmonary toxicity:

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Cardiopulmonary response Zn

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  1. Cardiopulmonary response Zn • INTRODUCTION (PM, Zn, ENaC) • Zn → ENaC↑ → (ASL and MCT)↓ • CONCLUSION

  2. Particulate matter (PM), Zn and Pulmonary and Systemic Toxicity • Zn soluble component of PM (ambient, combustion, emissions) critical for cardiopulmonary toxicity: Pulmonary: Smoke bomb, zinc fume fever Cardiovascular: dysrhythmia, MI, HT

  3. Zinc Cardiopulmonary Toxicity • essential metal (0.1-0.5 mM) • Zn-proteome: 3-10% • 24 Zn transporters • Zn as therapeutic agent

  4. Epithelial Sodium Channels (ENaC) • Mediate reabsorptive sodium transport across epithelial cell layers in conjunction with NaK-ATPase • Kidney: urinary Na+ reabsorption, ECF volume, blood pressure • Airway: regulate volume of airway surface liquid and MCT

  5. Zn increases sodium conductance in human airway epithelium

  6. Airway Epithelium cultured at Air-Liquid interface Cells labeled with cell-tracker green ASL labeled with texas-red dextran (10 kDa) ASL Height Measurement

  7. Drugs, Environmental toxins Heavy metals etc How do they effect clearance? Mucocilliary clearance

  8. Fluorescent beads 5 seconds/frame Primary airway culture 1 second/frame

  9. Efficient Mucus Clearance Requires Adequate ASL Volume

  10. Control 0.1 mM Zn External Zn2+ reduces mucociliary transport

  11. CONCLUSIONS • Zn → ENaC↑ → (ASL and MCT)↓ • Reconcile Zn impair host defense pathology of Zn deficiency therapeutic efficacy of Zn for flu • Molecular information utility in environmental health

  12. Pulmonary Endothelium • Claudette St. Croix • Paula Bernal • Karanee Leelavanichkul • Karla J. Wasserloos • Molly Stitt • Rong Cao • Song Li • Annette Wilson • Pulmonary Epithelium • Shaohu Sheng • Tom Kleyman • Mike Myerberg • Joe Pilewski • Phil Lamberty Simon Watkins, Center Biological Imaging

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