Imbalance in zinc homeostasis enhances lung tissue loss following cigarette smoke exposure.

Details

• Personal Author:
  Bao S ; Borchers MT ; Flury J ; Knoell DL ; Knutson M ; Sapkota M ; Smith, Denise L. ; Wyatt TA ; Zweier JL
• Description:
  Cigarette smoke exposure is a major cause of chronic obstructive pulmonary disease. Cadmium is a leading toxic component of cigarette smoke. Cadmium and zinc are highly related metals. Whereas, zinc is an essential metal required for normal health, cadmium is highly toxic. Zrt- and Irt-like protein 8 (ZIP8) is an avid transporter of both zinc and cadmium into cells and is abundantly expressed in the lung of smokers compared to nonsmokers. Our objective was to determine whether disturbed zinc homeostasis through diet or the zinc transporter ZIP8 increase susceptibility to lung damage following prolonged cigarette smoke exposure. Methods: Cigarette smoke exposure was evaluated in the lungs of mice subject to insufficient and sufficient zinc intakes, in transgenic ZIP8 overexpressing mice, and a novel myeloid-specific ZIP8 knockout strain. Results: Moderate depletion of zinc intakes in adult mice resulted in a significant increase in lung cadmium burden and permanent lung tissue loss following prolonged smoke exposure. Overexpression of ZIP8 resulted in increased lung cadmium burden and more extensive lung damage, whereas cigarette smoke exposure in ZIP8 knockout mice resulted in increased lung tissue loss without a change in lung cadmium content, but a decrease in zinc. Conclusions: Overall, findings were consistent with past human studies. Imbalance in Zn homeostasis increases susceptibility to permanent lung injury following prolonged cigarette smoke exposure. Based on animal studies, both increased and decreased ZIP8 expression enhanced irreversible tissue damage in response to prolonged tobacco smoke exposure. We believe these findings represent an important advancement in our understanding of how imbalance in zinc homeostasis and cadmium exposure via tobacco smoke may increase susceptibility to smoking-induced lung disease. [Description provided by NIOSH]
• Subjects:
  Animals Cadmium Diet Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety Smoke Smokers Tobacco Products

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• Keywords:
  Author Keywords: COPD; Zinc Transporter; Zinc; Cadmium; Cigarette Smoking Cigarette Smoking; Smoke Inhalation; Cadmium; Zinc; Lung Tissue; Animal Studies; Diet; Tobacco Smoke; Respiratory Diseases; COPD; Chronic Obstructive Pulmonary Disease;
• ISSN:
  0946-672X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Florida ; Nebraska ; Ohio ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  60
• NIOSHTIC Number:
  nn:20065150
• Citation:
  J Trace Elem Med Biol 2020 Jul; 60:126483
• Contact Point Address:
  Daren L. Knoell, College of Pharmacy, Room 2039 The University of Nebraska Medical Center 986120 Nebraska Medical Center, Omaha, NE, 68198-6120, United States
• Email:
  daren.knoell@unmc.edu
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9) ; Zinc (CAS RN 7440-66-6)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Journal of Trace Elements in Medicine and Biology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6528004c02032cc2ff3851d7931350609c98f5b92741c2e58055dee55a2673b1315e7615696bd5f5cbaeeb96b19d481683dd3b70e8c1349b02a598fc7be1859d
• Download URL:
  https://stacks.cdc.gov/view/cdc/249353/cdc_249353_DS1.pdf
• File Type:
  [PDF - 2.35 MB ]