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논문분류	춘계학술대회 초록집
제목	Atrial Natriuretic Peptide Prevented Lipid-Induced Kidney Injuries by Inhibiting Endoplasmic Reticulum Stress
저자	Xiaoduo Zhao, Yonglun Kong, Suchun Li, Boen Liang, Chunling Li, Weidong Wang
출판정보	2019; 2019(1):
키워드	ANP \| cGMP \| ER stress \| Kidney
초록	The purpose of the present study was to investigate whether atrial natriuretic peptide (ANP) prevented lipid-induced injury through inhibiting endoplasmic reticulum (ER) stress and apoptosis in the kidney. Western Blot, Real-time PCR, Immunofluorescence were performed In human proximal tubule HK2 cells, saturated fatty acid palmitic acid (PA) treatment (0.4mM) for 24h markedly increased protein abundance of two ER stress makers BiP (370% of controls) and CHOP (520% of controls), which was associated with upregulated cleaved-caspase 3 expression (320% of controls) and decreased ratio of Bcl2/Bax (76% of controls), two markers of apoptosis. ANP treatment (10pM) markedly decreased protein abundance of BiP (280% of controls), CHOP (370% of controls), and cleaved-caspase 3 (170% of controls), and increased the ratio of Bcl2/Bax (120% of controls) in HK2 cells treated by PA. Co-treatment with ANP and LBQ657, a neprilysin inhibitor preventing hydrolysis of ANP, showed better protective effects than ANP treatment alone in HK2 cells treated with PA. ANP is known to stimulate intracellular cGMP-PKG signaling pathway, roles of cGMP and PKG in ANP-induced protection were thus investigated. Sildenafil (an inhibitor of phosphadiesterase) and exogenous 8-Br-cGMP markedly suppressed PA-induced ER stress and apoptosis, whereas KT-5823, a selective cGMP-dependent PKG inhibitor, blocked protective effects of ANP or cGMP in HK2 cells treated with PA. Compared with controls, in mice fed with high-fat diet for 8wk, the protein expression of BiP and CHOP in the kidney cortex showed 2.8-fold and 2.3-fold increases, respectively, which was markedly prevented by sildenafil (15mg/kg·BW/day, gavage). In conclusion, our data demonstrated that ANP inhibited lipid-induced ER stress and apoptosis likely via activating the cGMP-PKG signaling pathway, and it may be a potentially therapeutic target for lipid-induced kidney injury.
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