Hsc70 and Hsp70 interact with phosphatidylserine on the surface of PC12 cells resulting in a decrease of viability.
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.
Arispe
Nelson
N
Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA. narispe@usuhs.mil
Doh
Michael
M
Simakova
Olga
O
Kurganov
Boris
B
De Maio
Antonio
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D016716:PC12 Cells; D010718:Phosphatidylserines / Q000032:analysis / Q000378:metabolism*; D051381:Rats
D017304:Annexin A5; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C494373:Hspa8 protein, rat; D010718:Phosphatidylserines; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate