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Study · In vitro (cells) · 2019

8 results

AMPK alleviates high uric acid-induced Na+-K+-ATPase signaling impairment and cell injury in renal tubules.

Xiao J, Zhu S, Guan H, Zheng Y, Li F, Zhang X, Guo H, Wang X, Ye Z

Experimental & molecular medicine22 May 2019Cited by 36 (Europe PMC)

PMID31118410 (opens in a new tab)PMCIDPMC6531502 (opens in a new tab)DOI10.1038/s12276-019-0254-y (opens in a new tab)PepBankPUB-31118410
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Summary

One of the mechanisms in hyperuricemia (HUA)-induced renal tubular injury is the impairment of Na+-K+-ATPase (NKA) signaling, which further triggers inflammation, autophagy, and mitochondrial dysfunction and leads to cell injury. Here, we used RNA sequencing to screen the most likely regulators of NKA signaling and found that the liver kinase B1(LKB1)/adenosine monophosphate (AMP)-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) pathway was the most abundantly enriched pathway in HUA. AMPK is a key regulator of cell energy metabolism; hence, we examined the effect of AMPK on HUA-induced dysregulation of NKA signaling and cell injury. We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs). We further found that sustained treatment with the AMPK activator 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR), but not the AMPK inhibitor Compound C, significantly alleviated UA-induced reductions in NKA activity and NKA α1 subunit expression on the cell membrane by reducing NKA degradation in lysosomes; sustained AICAR treatment also significantly alleviated activation of the NKA downstream molecules Src and interleukin-1β (IL-1β) in PTECs. AICAR further alleviated high UA-induced apoptosis, autophagy, and mitochondrial dysfunction. Although AMPK activation by metformin did not reduce serum UA levels in hyperuricemic rats, it significantly alleviated HUA-induced renal tubular injury and NKA signaling impairment in vivo with effects similar to those of febuxostat. Our study suggests that AMPK activation may temporarily compensate for HUA-induced renal injury. Sustained AMPK activation could reduce lysosomal NKA degradation and maintain NKA function, thus alleviating NKA downstream inflammation and protecting tubular cells from high UA-induced renal tubular injury.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In high uric acid-stimulated PTECs, sustained AICAR alleviated the reduction in NKA activity.

    In plain wordsIn cells exposed to high uric acid, AICAR preserved NKA activity compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseNKA activity
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We further found that sustained treatment with the AMPK activator 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR), but not the AMPK inhibitor Compound C, significantly alleviated UA-induced reductions in NKA activity and NKA α1 subunit expression on the cell membrane by reducing NKA degradation in lysosomes
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).
  2. 02LabIn vitro (cells)Mechanism

    In high uric acid-stimulated PTECs, sustained AICAR alleviated the reduction in membrane NKA α1 expression.

    In plain wordsIn cells exposed to high uric acid, AICAR preserved membrane NKA protein compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMembrane NKA α1 expression
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We further found that sustained treatment with the AMPK activator 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR), but not the AMPK inhibitor Compound C, significantly alleviated UA-induced reductions in NKA activity and NKA α1 subunit expression on the cell membrane by reducing NKA degradation in lysosomes
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).
  3. 03LabIn vitro (cells)Mechanism

    In high uric acid-stimulated PTECs, sustained AICAR reduced lysosomal NKA degradation.

    In plain wordsIn cells exposed to high uric acid, AICAR reduced NKA breakdown compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseLysosomal NKA degradation
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We further found that sustained treatment with the AMPK activator 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR), but not the AMPK inhibitor Compound C, significantly alleviated UA-induced reductions in NKA activity and NKA α1 subunit expression on the cell membrane by reducing NKA degradation in lysosomes
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).
  4. 04LabIn vitro (cells)Mechanism

    In high uric acid-stimulated PTECs, sustained AICAR alleviated Src activation.

    In plain wordsIn cells exposed to high uric acid, AICAR reduced Src activation compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseSrc activation
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    sustained AICAR treatment also significantly alleviated activation of the NKA downstream molecules Src and interleukin-1β (IL-1β) in PTECs.
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).
  5. 05LabIn vitro (cells)Mechanism

    In high uric acid-stimulated PTECs, sustained AICAR alleviated IL-1β activation.

    In plain wordsIn cells exposed to high uric acid, AICAR reduced IL-1β activation compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseIL-1β activation
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Inflammation markers · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    sustained AICAR treatment also significantly alleviated activation of the NKA downstream molecules Src and interleukin-1β (IL-1β) in PTECs.
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).
  6. 06LabIn vitro (cells)Efficacy outcome

    In PTECs, AICAR alleviated high uric acid-induced apoptosis.

    In plain wordsIn cells, AICAR reduced cell death caused by high uric acid compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseApoptosis
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AICAR further alleviated high UA-induced apoptosis, autophagy, and mitochondrial dysfunction.
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).
  7. 07LabIn vitro (cells)Mechanism

    In PTECs, AICAR alleviated high uric acid-induced autophagy.

    In plain wordsIn cells, AICAR reduced autophagy caused by high uric acid compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseAutophagy
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Receptor activity and mechanism · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AICAR further alleviated high UA-induced apoptosis, autophagy, and mitochondrial dysfunction.
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).
  8. 08LabIn vitro (cells)Efficacy outcome

    In PTECs, AICAR alleviated high uric acid-induced mitochondrial dysfunction.

    In plain wordsIn cells, AICAR reduced mitochondrial dysfunction caused by high uric acid compared with no AICAR.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseMitochondrial dysfunction
    Study

    n: not reported in source

    High uric acid-stimulated proximal tubular epithelial cells
    Comparator
    High uric acid without AICAR
    Outcome group
    Mitochondrial function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AICAR further alleviated high UA-induced apoptosis, autophagy, and mitochondrial dysfunction.
    1 context sentence
    Summary · context
    We first detected AMPK activation in high uric acid (UA)-stimulated proximal tubular epithelial cells (PTECs).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

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