Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury.
Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth(-/-)) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth(-/-) and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth(-/-) mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth(-/-) mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection.
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.|Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Lajos
L
Markó
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
István A
IA
Szijártó
Friedrich-Alexander-University of Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Erlangen, Germany.
Milos R
MR
Filipovic
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Mario
M
Kaßmann
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.|Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
András
A
Balogh
Hannover Medical School, Hannover, Germany.
Joon-Keun
JK
Park
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Lukasz
L
Przybyl
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Gabriele
G
N'diaye
German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
Stephanie
S
Krämer
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Juliane
J
Anders
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.
Isao
I
Ishii
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.|Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
Dominik N
DN
Müller
Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.|Charité Campus Virchow, Nephrology/Intensive Care, Berlin, Germany.
Maik
M
Gollasch
D058186:Acute Kidney Injury / Q000201:enzymology*; D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide