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泛素、p62和微管相关蛋白1轻链3与心肌病

Ubiquitin, p62, and Microtubule-Associated Protein 1 Light Chain 3 in Cardiomyopathy.

作者信息

Eto Ryo, Kawano Hiroaki, Matsuyama-Matsuu Mutsumi, Matsuda Katsuya, Ueki Nozomi, Nakashima Masahiro, Okano Shinji, Ishijima Mitsuaki, Kawakatsu Miho, Watanabe Jumpei, Yoshimuta Tsuyoshi, Ikeda Satoshi, Maemura Koji

机构信息

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan.

Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan.

出版信息

Circ Rep. 2023 Jul 6;5(8):323-330. doi: 10.1253/circrep.CR-23-0058. eCollection 2023 Aug 10.

DOI:10.1253/circrep.CR-23-0058
PMID:37564875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10411995/
Abstract

The accumulation of ubiquitinated proteins has been detected in diseased hearts and has been associated with the expression of p62 and microtubule-associated protein 1 light chain 3 (LC3), which are related to autophagy. We evaluated differences in ubiquitin accumulation and p62 and LC3 expression in cardiomyopathy using endomyocardial biopsies. We studied 24 patients (aged 24-70 years; mean age 55 years) diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or non-cardiomyopathy (NCM) who underwent endomyocardial biopsy. Biopsied samples were evaluated by microscopy for ubiquitin accumulation and expression of p62 and LC3. Ubiquitin accumulation and p62 and LC3 expression were observed in all patients. Ubiquitin accumulation was higher in DCM than in HCM or NCM; p62 expression was higher in DCM than in HCM. There were no significant differences in LC3 expression among the groups. Ubiquitin accumulation was significantly related to serum N-terminal pro B-type natriuretic peptide concentration and the expression of p62, but not LC3. Ubiquitin accumulation was more prominent in DCM than in HCM and NCM, which may be due to a relative shortage of clearance, including autophagy, compared with production.

摘要

在患病心脏中已检测到泛素化蛋白的积累，且其与自噬相关的p62和微管相关蛋白1轻链3（LC3）的表达有关。我们使用心内膜活检评估心肌病中泛素积累以及p62和LC3表达的差异。我们研究了24例接受心内膜活检的患者（年龄24 - 70岁；平均年龄55岁），他们被诊断为扩张型心肌病（DCM）、肥厚型心肌病（HCM）或非心肌病（NCM）。通过显微镜检查活检样本，评估泛素积累以及p62和LC3的表达。所有患者均观察到泛素积累以及p62和LC3表达。DCM中泛素积累高于HCM或NCM；DCM中p62表达高于HCM。各组间LC3表达无显著差异。泛素积累与血清N末端B型利钠肽原浓度以及p62的表达显著相关，但与LC3无关。DCM中泛素积累比HCM和NCM更显著，这可能是由于与产生相比，包括自噬在内的清除相对不足所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/9ee4f39c86cd/circrep-5-323-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/b22c4fd3c105/circrep-5-323-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/f82d9164dbc8/circrep-5-323-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/423a9666b9e1/circrep-5-323-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/ba88bf1bbf5d/circrep-5-323-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/9ee4f39c86cd/circrep-5-323-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/b22c4fd3c105/circrep-5-323-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/f82d9164dbc8/circrep-5-323-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/423a9666b9e1/circrep-5-323-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/ba88bf1bbf5d/circrep-5-323-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1d/10411995/9ee4f39c86cd/circrep-5-323-g005.jpg

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本文引用的文献

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CCT2 is an aggrephagy receptor for clearance of solid protein aggregates.CCT2 是一种用于清除固体蛋白聚集体的聚集体自噬受体。
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自噬对扩张型心肌病患者预后的影响。
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The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding.自噬蛋白 Becn1 通过与外泌体结合促进脂联素分泌，从而提高胰岛素敏感性。
Cell Rep. 2021 May 25;35(8):109184. doi: 10.1016/j.celrep.2021.109184.
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P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.P62 阳性聚集物均匀分布于心肌中，并与遗传性心肌病的突变类型相关。
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