Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement

Yugo Tanaka, Norihisa Shigemura, Tomohiro Kawamura, Kentaro Noda, Kumiko Isse, Donna Beer Stolz, Timothy R. Billiar, Yoshiya Toyoda, Christian A. Bermudez, James Lyons-Weiler, Atsunori Nakao

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 4. h 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)873-879
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number4
DOIs
Publication statusPublished - Sep 7 2012
Externally publishedYes

Fingerprint

Allografts
Hydrogen
Lung
Genes
Surface-Active Agents
Grafts
Transplants
Therapeutics
Adenosine Triphosphate
Reperfusion Injury
Molecules
Tissue
Cold Ischemia
Gene Expression
HSP70 Heat-Shock Proteins
Lung Transplantation
Artificial Respiration
Gene expression
Ventilation
Rats

Keywords

  • Adenosine triphosphate
  • Gene array
  • Hydrogen
  • Ischemia/reperfusion injury
  • Lung surfactant
  • Lung transplantation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement. / Tanaka, Yugo; Shigemura, Norihisa; Kawamura, Tomohiro; Noda, Kentaro; Isse, Kumiko; Stolz, Donna Beer; Billiar, Timothy R.; Toyoda, Yoshiya; Bermudez, Christian A.; Lyons-Weiler, James; Nakao, Atsunori.

In: Biochemical and Biophysical Research Communications, Vol. 425, No. 4, 07.09.2012, p. 873-879.

Research output: Contribution to journalArticle

Tanaka, Y, Shigemura, N, Kawamura, T, Noda, K, Isse, K, Stolz, DB, Billiar, TR, Toyoda, Y, Bermudez, CA, Lyons-Weiler, J & Nakao, A 2012, 'Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement', Biochemical and Biophysical Research Communications, vol. 425, no. 4, pp. 873-879. https://doi.org/10.1016/j.bbrc.2012.08.005
Tanaka, Yugo ; Shigemura, Norihisa ; Kawamura, Tomohiro ; Noda, Kentaro ; Isse, Kumiko ; Stolz, Donna Beer ; Billiar, Timothy R. ; Toyoda, Yoshiya ; Bermudez, Christian A. ; Lyons-Weiler, James ; Nakao, Atsunori. / Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 425, No. 4. pp. 873-879.
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abstract = "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 4. h 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. Conclusion: 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.",
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