PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes.
PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes.
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DOI：
10.1371/journal.pone.0009746
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发表时间：
2010-03-18
期刊：
影响因子：
3.7
通讯作者：
Matsubara H
中科院分区：
文献类型：
--
作者：
Isodono K;Takahashi T;Imoto H;Nakanishi N;Ogata T;Asada S;Adachi A;Ueyama T;Oh H;Matsubara H
为了鉴定心肌细胞中表达的新型跨膜和分泌分子，在大鼠新生心肌细胞中进行信号序列陷阱筛选。其中一个分子是跨膜蛋白，前列腺雄激素抑制信息-1（PARM-1）。虽然PARM-1已被鉴定为响应于去势在前列腺中诱导的基因，但其功能在很大程度上是未知的。我们的表达分析显示，PARM-1特异性表达于心脏和骨骼肌，并且在心脏中，心肌细胞表达PARM-1，但非心肌细胞不表达。免疫荧光染色显示PARM-1主要定位于内质网。在Dahl盐敏感大鼠中，高盐饮食导致高血压、心脏肥大和随后的心力衰竭，并显著刺激心脏中的PARM-1表达，同时伴随着ER应激标志物如GRP 78和CHOP的增加。在培养的心肌细胞中，PARM-1的表达被促炎细胞因子刺激，但不被肥大刺激。响应于ER应激诱导剂如毒胡萝卜素和衣霉素，观察到PARM-1表达的显著增加，其也诱导凋亡性细胞死亡。通过siRNA沉默PARM-1表达增强心肌细胞对ER应激的凋亡反应。PARM-1沉默还抑制PERK和ATF 6的表达，并增加CHOP的表达，而不影响IRE-1表达和JNK和Caspase-12活化。因此，PARM-1表达由ER应激诱导，其通过调节PERK、ATF 6和CHOP表达在心肌细胞中起保护作用。这些结果表明，PARM-1是一种新的ER跨膜分子，参与了高血压性心脏病的心脏重构。
To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1). While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER). In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease.
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影响因子：
8.3
作者：
Klotz, S;Hay, I;Burkhoff, D
通讯作者：
Burkhoff, D
DOI：
10.1152/ajpheart.00233.2008
发表时间：
2008-12-01
影响因子：
4.8
作者：
Asada, Satoshi;Takahashi, Tomosaburo;Oh, Hidemasa
通讯作者：
Oh, Hidemasa
影响因子：
6.4
作者：
Fladeby, Cathrine;Gupta, Shailly N.;Bakke, Oddmund
通讯作者：
Bakke, Oddmund
影响因子：
4.9
作者：
Doi, R;Masuyama, T;Hori, M
通讯作者：
Hori, M
影响因子：
20.1
作者：
Kitamura, Ryoji;Takahashi, Tomosaburo;Oh, Hidemasa
通讯作者：
Oh, Hidemasa