Kidney Week

Abstract: FR-PO941

Hydrogen Sulfide Ameliorates Aging Associated Kidney Changes in Mice

Session Information

• Geriatric Nephrology
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Geriatric Nephrology

• 901 Geriatric Nephrology

Authors

• Lee, Hak Joo, University of Texas Health Science Center, San Antonio, Texas, United States

Hak Joo Lee,

• Feliers, Denis, University of Texas Health Science Center, San Antonio, Texas, United States

Denis Feliers,

• Barnes, Jeffrey L., University of Texas Health Science Center, San Antonio, Texas, United States

Jeffrey L. Barnes,

• Oh, Sae Byeol, University of Texas Health Science Center, San Antonio, Texas, United States

Sae Byeol Oh,

• Ghosh-Choudhury, Goutam, University of Texas Health Science Center, San Antonio, Texas, United States

Goutam Ghosh-Choudhury,

• Galvan, Veronica, University of Texas Health Science Center, San Antonio, Texas, United States

Veronica Galvan,

• Strong, Randy, University of Texas Health Science Center, San Antonio, Texas, United States

Randy Strong,

• Nelson, James F, University of Texas Health Science Center, San Antonio, Texas, United States

James F Nelson,

• Salmon, Adam, University of Texas Health Science Center, San Antonio, Texas, United States

Adam Salmon,

• Kevil, Christopher G., Louisiana State University Health Science Center, Shreveport, Shreveport, Louisiana, United States

Christopher G. Kevil,

• Kasinath, Balakuntalam S., University of Texas Health Science Center, San Antonio, Texas, United States

Balakuntalam S. Kasinath,

Background

Hydrogen sulfide (H2S) ameliorates renal fibrosis and proteinuria in chronic kidney disease. We examined the status of H2S in kidney aging.

Methods

First study: The status of H2S metabolism and signaling pathways related to synthesis of proteins including matrix proteins were studied in renal cortical extracts from C57BL/6 male young (5 months old, n=10) vs. old mice (30 months old, n=10). Second study: We randomized 18-19 month-old male mice to receive NaHS in drinking water (30 μmoles/L) (NaHS group, n=20 mice) vs. water alone (Control group, n=14 mice) for 5 months.

Results

First study: Compared to young mice, increase in renal cortical laminin and type 1-collagen content in old mice was associated with decreased generation of H2S, increase in tyrosine phosphorylation of insulin receptor (IR) and IRS2, decrease in AMPK activity and activation of Akt-mTORC1-mRNA translation signaling axis. Second study: Administration of NaHS to 18-19 month-old mice increased plasma free sulfide levels. Food, water intake and body weights were similar and blood glucose normal in the two groups throughout the study duration. Systolic, diastolic, and mean blood pressures (BPs) were high at baseline and continued to rise in the Control group; NaHS reduced the BPs. NaHS abolished the progressive increase in urinary albumin to creatinine ratio seen in control mice and reduced serum cystatin C levels. NaHS inhibited the increase in renal cortical content of laminin and type 1-collagen and ameliorated the increase in glomerular fractional mesangial matrix volume. NaHS inhibited tyrosine phosphorylation of renal cortical IR and IRS-2. NaHS restored decreased AMPK activity to normal and inhibited the Akt-mTORC1-mRNA translation axis that leads to increase in protein synthesis. Aging mice showed increase in renal cortical monocyte infiltration and content of p21, IL-1β, IL-6, components of Senescence Associated Secretory Phenotype, SASP, which contribute to tissue injury; NaHS inhibited these changes.

Conclusion

Aging-induced kidney changes are associated with H2S deficiency. Administration of H2S ameliorates aging-induced kidney changes; the mechanisms appear to involve reduced hypertension, inhibition of signaling pathways leading to matrix protein synthesis, and SASP.

Funding

• Other NIH Support