Novel Potential Application of Chitosan Oligosaccharide for Attenuation of Renal Cyst Growth in the Treatment of Polycystic Kidney Disease

被引:6
作者
Pathomthongtaweechai, Nutthapoom [1 ]
Soodvilai, Sunhapas [2 ]
Pichyangkura, Rath [3 ]
Muanprasat, Chatchai [1 ]
机构
[1] Mahidol Univ, Fac Med, Chakri Naruebodindra Med Inst, Ramathibodi Hosp, Bang Phli 10540, Samut Prakan, Thailand
[2] Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand
[3] Chulalongkorn Univ, Fac Sci, Dept Biochem, Bangkok 10330, Thailand
来源
MOLECULES | 2020年 / 25卷 / 23期
关键词
chitosan oligosaccharide; renal cyst; polycystic kidney disease; AMP-activated protein kinase; drug discovery; CALCIUM-SENSING RECEPTOR; ACTIVATED PROTEIN-KINASE; IN-VITRO; DRUG CARRIERS; AMPK; DELIVERY; DEGRADATION; METABOLISM; MECHANISMS; CHITOOLIGOSACCHARIDE;
D O I
10.3390/molecules25235589
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chitosan oligosaccharide (COS), a natural polymer derived from chitosan, exerts several biological activities including anti-inflammation, anti-tumor, anti-metabolic syndrome, and drug delivery enhancer. Since COS is vastly distributed to kidney and eliminated in urine, it may have a potential advantage as the therapeutics of kidney diseases. Polycystic kidney disease (PKD) is a common genetic disorder characterized by multiple fluid-filled cysts, replacing normal renal parenchyma and leading to impaired renal function and end-stage renal disease (ESRD). The effective treatment for PKD still needs to be further elucidated. Interestingly, AMP-activated protein kinase (AMPK) has been proposed as a drug target for PKD. This study aimed to investigate the effect of COS on renal cyst enlargement and its underlying mechanisms. We found that COS at the concentrations of 50 and 100 mu g/mL decreased renal cyst growth without cytotoxicity, as measured by MTT assay. Immunoblotting analysis showed that COS at 100 mu g/mL activated AMPK, and this effect was abolished by STO-609, a calcium/calmodulin-dependent protein kinase kinase beta (CaMKK beta) inhibitor. Moreover, COS elevated the level of intracellular calcium. These results suggest that COS inhibits cyst progression by activation of AMPK via CaMKK beta. Therefore, COS may hold the potential for pharmaceutical application in PKD.
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页数:12
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