|Degradation of leucine zipper-positive isoform of MYPT1 may contribute to development of nitrate tolerance|
|Dou, Dou1,2; Ma, Huijuan1; Zheng, Xiaoxu1; Ying, Lei1; Guo, Yixuan1; Yu, Xiaoxing1; Gao, Yuansheng1,2|
|关键词||PKG Myosin light chain phosphatase Proteasome|
|WOS标题词||Science & Technology|
|类目[WOS]||Cardiac & Cardiovascular Systems|
|研究领域[WOS]||Cardiovascular System & Cardiology|
|关键词[WOS]||DEPENDENT PROTEIN-KINASE ; LIGHT-CHAIN PHOSPHATASE ; MITOCHONDRIAL ALDEHYDE DEHYDROGENASE ; SMOOTH-MUSCLE RELAXATION ; NITRIC-OXIDE ; MYOSIN PHOSPHATASE ; CYCLIC-GMP ; NITROGLYCERIN TOLERANCE ; GLYCERYL TRINITRATE ; GUANYLATE-CYCLASE|
A depressed cGMP-dependent protein kinase (PKG) activity is implicated in nitrate tolerance. The present study determines whether the leucine zipper-positive (LZ+) isoform of myosin phosphatase target subunit 1 (MYPT1), a key target protein for PKG actions, is involved in the development of nitrate tolerance.
Nitrate tolerance in in vitro preparations was obtained by a 24 h incubation with nitroglycerin (NTG). Nitrate tolerance in in vivo preparations was obtained by subcutaneous injection of mice with NTG, and the aortas were used. Protein levels of total MYPT1, MYPT1 (LZ+), PP1C delta, myosin light chain (MLC), and phosphorylated MLC were determined by Western blot analysis. Isometric vessel tension was determined by an organ chamber technique. Protein levels of MYPT1 (LZ+), but not of PP1C delta, were significantly reduced in in vitro and in vivo nitrate-tolerant arteries. The decrease in the MYPT1 (LZ+) protein level of coronary artery was also induced by a nitric oxide donor and a cGMP analogue, which was prevented by the inhibitors of soluble guanylyl cyclase and PKG. The decrease in MYPT1 (LZ+) protein levels was not affected by the inhibitor of protein synthesis, but was prevented by the inhibitors of proteasomes. The diminished inhibition of dephosphorylation of MLC as well as the attenuated relaxation of porcine coronary artery and mouse aorta to NTG was improved by proteasome inhibitors.
This study demonstrates that a reduction in the protein level of MYPT1 (LZ+) is involved in nitrate tolerance. This may result in part from a proteasome-dependent degradation of MYPT1 (LZ+).
|项目编号||30770789 ; 30870938 ; 2006CB503802|
|资助机构||National Natural Science Foundation of China ; Major National Basic Research Program of China|
|作者单位||1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China|
2.Peking Univ, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
|Dou, Dou,Ma, Huijuan,Zheng, Xiaoxu,et al. Degradation of leucine zipper-positive isoform of MYPT1 may contribute to development of nitrate tolerance[J]. CARDIOVASCULAR RESEARCH,2010,86(1):151-159.|
|APA||Dou, Dou.,Ma, Huijuan.,Zheng, Xiaoxu.,Ying, Lei.,Guo, Yixuan.,...&Gao, Yuansheng.(2010).Degradation of leucine zipper-positive isoform of MYPT1 may contribute to development of nitrate tolerance.CARDIOVASCULAR RESEARCH,86(1),151-159.|
|MLA||Dou, Dou,et al."Degradation of leucine zipper-positive isoform of MYPT1 may contribute to development of nitrate tolerance".CARDIOVASCULAR RESEARCH 86.1(2010):151-159.|
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