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Kidney Week

Abstract: PO0347

A Mitochondrial Cardiolipin Targeting Peptide Ameliorates Kidney Oxidative Damage

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kwon, Soie, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Cho, Semin, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Moon, Jong joo, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Kim, Kyu hong, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Lee, Jae Wook, National Cancer Center, Goyang, Gyeonggi-do, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Kim, Yon Su, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Yang, Seung Hee, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
Background

Mitochondria is a major organelle of adenosine triphosphate production and O2 consumption. Also, kidney is mitochondria abundant organ. Many mitochondria-targeting agents were developed, though there is no single agent approved in clinical practice. We investigate renoprotective effect of newly invented mitochondrial cardiolipin targeting peptide, the SNU-RD, in hypoxic condition.

Methods

Based on our experience that dimer formation by bisulfate bond of cell penetrating peptide accelerate cell permeability, we synthesized 15 candidate tetra-peptides which target inner mitochondrial membrane specific phospholipid, the cardiolipin. After cell viability, distribution and mitochondrial functional test, we selected best candidate and tentatively named as SNU-RD.
As hypoxic damage, bilateral ischemia-reperfusion injury (IRI) and primary cultured human proximal tubular epithelial cells (hPTECs) with H2O2 were chosen. Wild-type mice were divided into four groups: sham, IRI, IRI with low dose or high dose SNU-RD. After SNU-RD treatment with various concentration (10nM, 100nM, 1000nM), high dose H2O2 stress was done. Mitochondrial function was tested and mitochondrial oxygen consumption rate (OCR) was measured.

Results

In IRI, serum BUN and creatinine were significantly decreased without SNU-RD dose dependency. Pathologic findings (NGAL and cytochrome C) were improved. Also, mitochondrial anti-oxidative enzyme (NQO-1, SOD-1), ATP6 and IL-10 mRNAs were over-expressed after SNU-RD treatment.
Cell viability was increased with dose dependently decrease of early and late apoptosis. IL-1ß, IL-18, p16 and p21 mRNA were dramatically down-regulated. When traced by rhodamine, SNU-RD was intensively distributed to mitochondria then cytoplasm. In JC-1 assay, ratio of healthy mitochondria was increased with SNU-RD. Basal and maximal OCR were most recovered from SNU-RD 10nM.

Conclusion

Mitochondrial cardiolipin targeting peptide, SNU-RD can protect kidney from hypoxic injury by restoring mitochondrial function.