Arispe Nelson, Doh Michael, Simakova Olga, Kurganov Boris, De Maio Antonio
Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
FASEB J. 2004 Nov;18(14):1636-45. doi: 10.1096/fj.04-2088com.
Heat shock proteins (hsps) are involved in multiple cellular processes during normal and stress conditions, particularly in the folding of polypeptides. A newly recognized property of the members of the Hsp70 family is their ability to interact with lipids, opening ion conductance pathways in artificial membranes, and integrating into natural membranes. The formation of Hsp70 channels in biological membranes and their function is still elusive. In this study, we showed that Hsp70 and Hsc70 display a highly selective interaction with phosphatidylserine moieties on membranes, followed by rapid incorporation into the lipid bilayer. Addition of Hsp70 or Hsc70 into the extracellular medium resulted in a viability decrease of cells beading PS on the exterior surface, such as PC12 cells. This toxic effect is modulated by the presence of ATP or ADP and can be blocked by screening PS moieties with annexin 5. These observations suggest that the presence of Hsp70 in the extracellular medium may be an accelerator of apoptosis since the presence of PS on the surface is an early indicator of this process. These findings may also explain the toxicity observed in cells overexpressing Hsp70s and provide a rational for the tight regulation of Hsp70 expression.
热休克蛋白（hsps）在正常和应激条件下参与多种细胞过程，尤其是在多肽折叠方面。Hsp70家族成员的一个新发现的特性是它们与脂质相互作用的能力，能在人工膜中打开离子传导通道，并整合到天然膜中。生物膜中Hsp70通道的形成及其功能仍然不清楚。在本研究中，我们表明Hsp70和Hsc70与膜上的磷脂酰丝氨酸部分表现出高度选择性相互作用，随后迅速整合到脂质双层中。将Hsp70或Hsc70添加到细胞外培养基中会导致外表面带有PS的细胞（如PC12细胞）活力下降。这种毒性作用受ATP或ADP的存在调节，并且可以通过用膜联蛋白5筛选PS部分来阻断。这些观察结果表明，细胞外培养基中Hsp70的存在可能是细胞凋亡的促进因素，因为表面存在PS是该过程的早期指标。这些发现也可能解释在过表达Hsp70的细胞中观察到的毒性，并为严格调控Hsp70表达提供了理论依据。
