Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy

Junichiro Yamamoto, Waichi Sato, Tomoki Kosugi, Tokunori Yamamoto, Toshihide Kimura, Shigeki Taniguchi, Hiroshi Kojima, Shoichi Maruyama, Enyu Imai, Seiichi Matsuo, Yukio Yuzawa, Ichiro Niki

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Abstract

Background: Hydrogen sulfide (H2S) has recently been found to play beneficial roles in ameliorating several diseases, including hypertension, atherosclerosis and cardiac/renal ischemia-reperfusion injuries. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the main enzymes in the transsulfuration pathway, catalyze H2S production in mammalian tissues. However, the distributions and precise roles of these enzymes in the kidney have not yet been identified. Methods: The present study examined the localization of both enzymes in the normal kidney and the effect of the H 2S donor sodium hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of diabetic nephropathy, using pancreatic β-cell-specific calmodulin-overexpressing transgenic mice as a model of diabetes. Results: In the normal kidney, we detected expression of both CBS and CSE in the brush border and cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC diameter and blood flow. We further evaluated whether biosynthesis of H2S was altered in a spontaneous diabetic model that developed renal lesions similar to human diabetic nephropathy. CSE expression was markedly reduced under diabetic conditions, whereas CBS expression was unaffected. Progressive diabetic nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was ameliorated by NaHS treatment. Conclusion: These findings suggest that CSE expression in the proximal tubules may also regulate tubulointerstitial microcirculation via H2S production. H2S may represent a target of treatment to prevent progression of ischemic injury in diabetic nephropathy.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalClinical and Experimental Nephrology
Volume17
Issue number1
DOIs
Publication statusPublished - 01-02-2013

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Hydrogen Sulfide
Diabetic Nephropathies
Cystathionine
Lyases
Kidney
Enzymes
Factor IX
Calmodulin
Microcirculation
Microvilli
sodium bisulfide
Vasoconstriction
Reperfusion Injury
Transgenic Mice
Atherosclerosis
Cytoplasm
Endothelial Cells
Hypertension
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Yamamoto, Junichiro ; Sato, Waichi ; Kosugi, Tomoki ; Yamamoto, Tokunori ; Kimura, Toshihide ; Taniguchi, Shigeki ; Kojima, Hiroshi ; Maruyama, Shoichi ; Imai, Enyu ; Matsuo, Seiichi ; Yuzawa, Yukio ; Niki, Ichiro. / Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy. In: Clinical and Experimental Nephrology. 2013 ; Vol. 17, No. 1. pp. 32-40.
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abstract = "Background: Hydrogen sulfide (H2S) has recently been found to play beneficial roles in ameliorating several diseases, including hypertension, atherosclerosis and cardiac/renal ischemia-reperfusion injuries. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the main enzymes in the transsulfuration pathway, catalyze H2S production in mammalian tissues. However, the distributions and precise roles of these enzymes in the kidney have not yet been identified. Methods: The present study examined the localization of both enzymes in the normal kidney and the effect of the H 2S donor sodium hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of diabetic nephropathy, using pancreatic β-cell-specific calmodulin-overexpressing transgenic mice as a model of diabetes. Results: In the normal kidney, we detected expression of both CBS and CSE in the brush border and cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC diameter and blood flow. We further evaluated whether biosynthesis of H2S was altered in a spontaneous diabetic model that developed renal lesions similar to human diabetic nephropathy. CSE expression was markedly reduced under diabetic conditions, whereas CBS expression was unaffected. Progressive diabetic nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was ameliorated by NaHS treatment. Conclusion: These findings suggest that CSE expression in the proximal tubules may also regulate tubulointerstitial microcirculation via H2S production. H2S may represent a target of treatment to prevent progression of ischemic injury in diabetic nephropathy.",
author = "Junichiro Yamamoto and Waichi Sato and Tomoki Kosugi and Tokunori Yamamoto and Toshihide Kimura and Shigeki Taniguchi and Hiroshi Kojima and Shoichi Maruyama and Enyu Imai and Seiichi Matsuo and Yukio Yuzawa and Ichiro Niki",
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Yamamoto, J, Sato, W, Kosugi, T, Yamamoto, T, Kimura, T, Taniguchi, S, Kojima, H, Maruyama, S, Imai, E, Matsuo, S, Yuzawa, Y & Niki, I 2013, 'Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy', Clinical and Experimental Nephrology, vol. 17, no. 1, pp. 32-40. https://doi.org/10.1007/s10157-012-0670-y

Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy. / Yamamoto, Junichiro; Sato, Waichi; Kosugi, Tomoki; Yamamoto, Tokunori; Kimura, Toshihide; Taniguchi, Shigeki; Kojima, Hiroshi; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Yuzawa, Yukio; Niki, Ichiro.

In: Clinical and Experimental Nephrology, Vol. 17, No. 1, 01.02.2013, p. 32-40.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy

AU - Yamamoto, Junichiro

AU - Sato, Waichi

AU - Kosugi, Tomoki

AU - Yamamoto, Tokunori

AU - Kimura, Toshihide

AU - Taniguchi, Shigeki

AU - Kojima, Hiroshi

AU - Maruyama, Shoichi

AU - Imai, Enyu

AU - Matsuo, Seiichi

AU - Yuzawa, Yukio

AU - Niki, Ichiro

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Background: Hydrogen sulfide (H2S) has recently been found to play beneficial roles in ameliorating several diseases, including hypertension, atherosclerosis and cardiac/renal ischemia-reperfusion injuries. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the main enzymes in the transsulfuration pathway, catalyze H2S production in mammalian tissues. However, the distributions and precise roles of these enzymes in the kidney have not yet been identified. Methods: The present study examined the localization of both enzymes in the normal kidney and the effect of the H 2S donor sodium hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of diabetic nephropathy, using pancreatic β-cell-specific calmodulin-overexpressing transgenic mice as a model of diabetes. Results: In the normal kidney, we detected expression of both CBS and CSE in the brush border and cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC diameter and blood flow. We further evaluated whether biosynthesis of H2S was altered in a spontaneous diabetic model that developed renal lesions similar to human diabetic nephropathy. CSE expression was markedly reduced under diabetic conditions, whereas CBS expression was unaffected. Progressive diabetic nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was ameliorated by NaHS treatment. Conclusion: These findings suggest that CSE expression in the proximal tubules may also regulate tubulointerstitial microcirculation via H2S production. H2S may represent a target of treatment to prevent progression of ischemic injury in diabetic nephropathy.

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