Daren L Knoell1, Deandra Smith2, Shengying Bao3, Muna Sapkota4, Todd A Wyatt5, Jay L Zweier6, Jennifer Flury7, Michael T Borchers8, Mitch Knutson9. 1. The University of Nebraska Medical Center College of Pharmacy, Omaha, NE, 68198, United States. Electronic address: daren.knoell@unmc.edu. 2. The University of Nebraska Medical Center College of Pharmacy, Omaha, NE, 68198, United States. Electronic address: deandra.smith@unmc.edu. 3. The Ohio State University College of Medicine, Columbus, OH, 43210, United States. Electronic address: Shengying.Bao@osumc.edu. 4. The University of Nebraska Medical Center College of Pharmacy, Omaha, NE, 68198, United States. Electronic address: muna.sapkota@unmc.edu. 5. The University of Nebraska Medical Center College of Public Health, Omaha, NE, 68198, United States; VA Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, United States. Electronic address: twyatt@unmc.edu. 6. The Ohio State University College of Medicine, Columbus, OH, 43210, United States. Electronic address: Jay.Zweier@osumc.edu. 7. The University of Cincinnati Department of Internal Medicine, United States. 8. The University of Cincinnati Department of Internal Medicine, United States. Electronic address: Borchemt@ucmail.uc.edu. 9. The University of Florida Food Science and Nutrition Institute, United States. Electronic address: mknutson@ufl.edu.
Abstract
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.
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.
Authors: Claire Healy; Natalia Munoz-Wolf; Janné Strydom; Lynne Faherty; Niamh C Williams; Sarah Kenny; Seamas C Donnelly; Suzanne M Cloonan Journal: Respir Res Date: 2021-04-29
Authors: Anatoly V Skalny; Thania Rios Rossi Lima; Tao Ke; Ji-Chang Zhou; Julia Bornhorst; Svetlana I Alekseenko; Jan Aaseth; Ourania Anesti; Dimosthenis A Sarigiannis; Aristides Tsatsakis; Michael Aschner; Alexey A Tinkov Journal: Food Chem Toxicol Date: 2020-10-16 Impact factor: 6.023