Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement.
BACKGROUND
We previously demonstrated that donor treatment with inhaled hydrogen protects lung grafts from cold ischemia/reperfusion (I/R) injury during lung transplantation. To elucidate the mechanisms underlying hydrogen's protective effects, we conducted a gene array analysis to identify changes in gene expression associated with hydrogen treatment.


METHODS
Donor rats were exposed to mechanical ventilation with 98% oxygen and 2% nitrogen or 2% hydrogen for 3 h before harvest; lung grafts were stored for 4h in cold Perfadex. Affymetrix gene array analysis of mRNA transcripts was performed on the lung tissue prior to implantation.


RESULTS
Pretreatment of donor lungs with hydrogen altered the expression of 229 genes represented on the array (182 upregulated; 47 downregulated). Hydrogen treatment induced several lung surfactant-related genes, ATP synthase genes and stress-response genes. The intracellular surfactant pool, tissue adenosine triphosphate (ATP) levels and heat shock protein 70 (HSP70) expression increased in the hydrogen-treated grafts. Hydrogen treatment also induced the transcription factors C/EBPα and C/EBPβ, which are known regulators of surfactant-related genes.


CONCLUSIONS
Donor ventilation with hydrogen significantly increases expression of surfactant-related molecules, ATP synthases and stress-response molecules in lung grafts. The induction of these molecules may underlie hydrogen's protective effects against I/R injury during transplantation.
Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Yugo
Y
Tanaka
Norihisa
N
Shigemura
Tomohiro
T
Kawamura
Kentaro
K
Noda
Kumiko
K
Isse
Donna Beer
DB
Stolz
Timothy R
TR
Billiar
Yoshiya
Y
Toyoda
Christian A
CA
Bermudez
James
J
Lyons-Weiler
Atsunori
A
Nakao
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D006859:Hydrogen / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D016040:Lung Transplantation; D008297:Male; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D012121:Respiration, Artificial; D013312:Stress, Physiological / Q000235:genetics; D020858:Tissue and Organ Harvesting / Q000379:methods*; D009927:Tissue and Organ Procurement; D059467:Transcriptome
D022762:CCAAT-Enhancer-Binding Proteins; D037661:Pulmonary Surfactant-Associated Proteins; D006859:Hydrogen