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  • Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a Nrf‑2‑dependent manner.

Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a Nrf‑2‑dependent manner.

Molecular medicine reports (2021-07-24)
Wen-Juan Wang, Xia Jiang, Chang-Chun Gao, Zhi-Wei Chen
ABSTRACT

Ferroptosis is critically involved in the pathophysiology of diabetic nephropathy (DN). As a bioactive peptide, salusin‑β is abundantly expressed in the kidneys. However, it is unclear whether salusin‑β participates in the pathologies of diabetic kidney damage by regulating ferroptosis. The present study found that high glucose (HG) treatment upregulated the protein expressions of salusin‑β in a dose‑ and time‑dependent manner. Genetic knockdown of salusin‑β retarded, whereas overexpression of salusin‑β aggravated, HG‑triggered iron overload, antioxidant capability reduction, massive reactive oxygen species production and lipid peroxidation in HK‑2 cells. Mechanistically, salusin‑β inactivated nuclear factor erythroid‑derived 2‑like 2 (Nrf‑2) signaling, thus contributing to HG‑induced ferroptosis‑related changes in HK‑2 cells. Notably, the protein expression of salusin‑β was upregulated by ferroptosis activators, such as erastin, RSL3, FIN56 and buthionine sulfoximine. Pretreatment with ferrostatin‑1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin‑β in HK‑2 cells exposed to HG. Taken together, these results suggested that a positive feedback loop between salusin‑β and ferroptosis primes renal tubular cells for injury in diabetes.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2′,7′-Dichlorofluorescin diacetate, ≥97%
Sigma-Aldrich
D-Mannitol, ≥98%
Sigma-Aldrich
Ferrostatin-1, ≥95% (HPLC)
Sigma-Aldrich
Erastin, ≥98% (HPLC)
Sigma-Aldrich
L-Buthionine-sulfoximine, ≥97% (TLC)
Sigma-Aldrich
4′,6-Diamidino-2-phenylindole dihydrochloride, powder, BioReagent, suitable for cell culture, ≥98% (HPLC and TLC), suitable for fluorescence
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC)