TAT-Hsp40 inhibits oxidative stress-mediated cytotoxicity via the inhibition of Hsp70 ubiquitination.
Heat shock protein 40 (Hsp40) functions as a co-chaperone of mammalian Heat shock protein 70 (Hsp70) and facilitates the ATPase activity of Hsp70, and also promotes the cellular protein folding and renaturation of misfolded proteins. In an effort to assess the effects of Hsp40, we generated TAT-fused Hsp40 (TAT-Hsp40). The cells were transduced with TAT-Hsp40 and exposed to H(2)O(2). We demonstrated that the TAT-Hsp40-transduced cells were more resistant to cellular cytotoxicity and cell death. In particular, the degradation of Hsp70 was significantly reduced in TAT-Hsp40-containing cells as a consequence of reduced ubiquitin-proteasome activity after oxidative injury. These data support the notion that Hsp40 may confer resistance to oxidative stress via the prevention of proteasome activity.
Kim
Soo-A
SA
Department of Biochemistry, Dongguk University College of Oriental Medicine, Gyeongju, South Korea.
Chang
Sunghoe
S
Yoon
Jung-Hoon
JH
Ahn
Sang-Gun
SG
D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D005434:Flow Cytometry; D050956:HSP40 Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism*; D013696:Temperature; D014161:Transduction, Genetic; D054875:Ubiquitination / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000302:isolation & purification / Q000378:metabolism*
D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D061988:Proteasome Inhibitors; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D006861:Hydrogen Peroxide