Cell-penetrating peptides induce apoptosis and necrosis through specific mechanism and cause impairment of Na⁺–K⁺-ATPase and mitochondria

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• 作者：Yue Qiu ; Qianwen Yu ; Kairong Shi ; Mengmeng Zhang ; Xianyang Zhou ; Yuting Yang…
• 关键词：Cell ; penetrating peptide ; Necrosis ; Apoptosis ; Na+–K+ ; ATPase ; Mitochondria
• 刊名：Amino Acids
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：49
• 期：1
• 页码：75-88
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Analytical Chemistry; Biochemical Engineering; Life Sciences, general; Proteomics; Neurobiology;
• 出版者：Springer Vienna
• ISSN：1438-2199
• 卷排序：49

文摘

Cell-penetrating peptides (CPPs) are widely used in the development of various drug delivery systems because of their ability of penetrating plasma membrane. However, the safety of their application remains largely unknown. In this study, we found that the incubation of two main kinds of CPPs with human normal liver cells could cause the occurrence of apoptosis and necrosis, then the detailed apoptosis-related protein were detected out. To discover the specific way which leads to these results, several methods were used in this study. Several cytokines, such as Caspase3 and Bcl-2, were detected to prove that the damage happened after treated with different CPPs. Then shielding the positive charge of TAT and R8, depletion of Na+ in culturing medium and addition of several inhibitors of specific ATPase site were used to investigate whether the cytotoxicity were charge-dependent and ATPase-related. Furthermore, the membrane potential of mitochondria and the leakage of mitochondrial cytochrome c were detected after treated with CPPs to investigate the damage on mitochondria. In general, our results assess the cytotoxicity caused by two main kinds of CPPs and reveal the clear mechanism of how it occurs. This study reveals the essence of cytotoxicity caused by CPPs, and the methods we followed can be used to evaluate the biocompatibility of new-designed CPPs, which makes the application of CPPs better and safer.