Polyarginine Cell-Penetrating Peptides Bind and Inhibit SERCA2

磷化氢 农奴 内质网 化学 基因亚型 细胞质 细胞生物学 胞浆 生物物理学 细胞 心肌细胞 生物化学 ATP酶 生物 基因
作者
Per Lunde,Ornella Manfra,Thea Parsberg Støle,Marianne Lunde,Marita Martinsen,Cathrine R. Carlson,William E. Louch
出处
期刊:Cells [Multidisciplinary Digital Publishing Institute]
卷期号:12 (19): 2358-2358
标识
DOI:10.3390/cells12192358
摘要

Cell-penetrating peptides (CPPs) are short peptide sequences that have the ability to cross the cell membrane and deliver cargo. Although it is critical that CPPs accomplish this task with minimal off-target effects, such actions have in many cases not been robustly screened. We presently investigated whether the commonly used CPPs TAT and the polyarginines Arg9 and Arg11 exert off-target effects on cellular Ca2+ homeostasis. In experiments employing myocytes and homogenates from the cardiac left ventricle or soleus muscle, we observed marked inhibition of Ca2+ recycling into the sarcoplasmic reticulum (SR) following incubation with polyarginine CPPs. In both tissues, the rate of SR Ca2+ leak remained unchanged, indicating that protracted Ca2+ removal from the cytosol stemmed from inhibition of the SR Ca2+ ATPase 2 (SERCA2). No such inhibition occurred following treatment with TAT, or in preparations from the SERCA1-expressing extensor digitorum longus muscle. Experiments in HEK cells overexpressing individual SERCA isoforms confirmed that polyarginine incubation specifically inhibited the activity of SERCA2a and 2b, but not SERCA1 or 3. The attenuation of SERCA2 activity was not dependent on the presence of phospholamban, and ELISA-based analyses rather revealed direct interaction between the polyarginines and the actuator domain of the protein. Surface plasmon resonance experiments confirmed strong binding within this region of SERCA2, and slow dissociation between the two species. Based on these observations, we urge caution when employing polyarginine CPPs. Indeed, as SERCA2 is expressed in diverse cell types, the wide-ranging consequences of SERCA2 binding and inhibition should be anticipated in both experimental and therapeutic settings.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
研友_VZG7GZ应助陈纸溪采纳,获得10
刚刚
搞怪城发布了新的文献求助10
刚刚
小杨完成签到 ,获得积分10
1秒前
彭于晏应助愉快的宛儿采纳,获得10
2秒前
4秒前
沉默高跟鞋完成签到,获得积分10
5秒前
wanci应助无算浮白采纳,获得10
5秒前
oh关闭了oh文献求助
5秒前
6秒前
7秒前
8秒前
ncxxxxx发布了新的文献求助10
8秒前
8秒前
10秒前
10秒前
10秒前
Dog完成签到,获得积分10
11秒前
12秒前
赘婿应助明亮访烟采纳,获得10
12秒前
搜集达人应助科研通管家采纳,获得10
13秒前
求知者1701应助科研通管家采纳,获得10
13秒前
13秒前
研友_VZG7GZ应助科研通管家采纳,获得10
14秒前
orixero应助科研通管家采纳,获得10
14秒前
ding应助科研通管家采纳,获得10
14秒前
Jasper应助科研通管家采纳,获得10
14秒前
TTZ发布了新的文献求助30
14秒前
科研通AI5应助科研通管家采纳,获得10
14秒前
所所应助科研通管家采纳,获得10
14秒前
沛山应助科研通管家采纳,获得10
14秒前
wanci应助科研通管家采纳,获得10
14秒前
14秒前
英姑应助科研通管家采纳,获得10
14秒前
沛山应助科研通管家采纳,获得10
14秒前
14秒前
沛山应助科研通管家采纳,获得10
15秒前
思源应助科研通管家采纳,获得10
15秒前
充电宝应助科研通管家采纳,获得10
15秒前
沛山应助科研通管家采纳,获得10
15秒前
大模型应助科研通管家采纳,获得10
15秒前
高分求助中
(应助此贴封号)【重要!!请各位详细阅读】【科研通的精品贴汇总】 10000
줄기세포 생물학 1000
Biodegradable Embolic Microspheres Market Insights 888
Quantum reference frames : from quantum information to spacetime 888
Pediatric Injectable Drugs 500
Instant Bonding Epoxy Technology 500
ASHP Injectable Drug Information 2025 Edition 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4406385
求助须知:如何正确求助?哪些是违规求助? 3891665
关于积分的说明 12110778
捐赠科研通 3536652
什么是DOI,文献DOI怎么找? 1940644
邀请新用户注册赠送积分活动 981442
科研通“疑难数据库(出版商)”最低求助积分说明 877965