Abstract
Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H2S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H2S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H2S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18–19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H2S deficiency. Administration of H2S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-14 |
| Number of pages | 14 |
| Journal | GeroScience |
| DOIs | |
| State | Accepted/In press - May 1 2018 |
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Keywords
- AMP-activated protein kinase
- Insulin receptor signaling
- Mechanistic target of rapamycin
- Protein chemistry
ASJC Scopus subject areas
- Aging
- Geriatrics and Gerontology
Cite this
Hydrogen sulfide ameliorates aging-associated changes in the kidney. / Lee, Hak Joo; Feliers, Denis; Barnes, Jeffrey L.; Oh, Sae; Ghosh-choudhury, Goutam; Diaz, Vivian; Galvan Hart, Veronica; Strong, John R; Nelson, James F; Salmon, Adam; Kevil, Christopher G.; Kasinath, Balakuntalam S.
In: GeroScience, 01.05.2018, p. 1-14.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hydrogen sulfide ameliorates aging-associated changes in the kidney
AU - Lee, Hak Joo
AU - Feliers, Denis
AU - Barnes, Jeffrey L.
AU - Oh, Sae
AU - Ghosh-choudhury, Goutam
AU - Diaz, Vivian
AU - Galvan Hart, Veronica
AU - Strong, John R
AU - Nelson, James F
AU - Salmon, Adam
AU - Kevil, Christopher G.
AU - Kasinath, Balakuntalam S
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H2S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H2S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H2S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18–19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H2S deficiency. Administration of H2S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.
AB - Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H2S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H2S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H2S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18–19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H2S deficiency. Administration of H2S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.
KW - AMP-activated protein kinase
KW - Insulin receptor signaling
KW - Mechanistic target of rapamycin
KW - Protein chemistry
UR - http://www.scopus.com/inward/record.url?scp=85046147195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046147195&partnerID=8YFLogxK
U2 - 10.1007/s11357-018-0018-y
DO - 10.1007/s11357-018-0018-y
M3 - Article
SP - 1
EP - 14
JO - GeroScience
JF - GeroScience
SN - 2509-2715
ER -