Overexpression of mitochondrial Hsp70/Hsp75 protects astrocytes against ischemic injury in vitro.
Mitochondrial heat shock protein 70 (mtHsp70/Hsp75/Grp75/mortalin/TRAP-1/PBP74) is an essential mitochondrial chaperone and a member of the heat shock protein 70 (HSP70) family. Although many studies have shown the protective properties of overexpression of the cytosolic inducible member of the HSP70 family, Hsp72, few studies have investigated the protective potential of Hsp75 against ischemic injury. Mitochondria are one of the primary targets of ischemic injury in astrocytes. In this study, we analyzed the effects of Hsp75 overexpression on cellular levels of reactive oxygen species (ROS), mitochondrial membrane potential, ATP levels, and viability during the ischemia-like conditions of oxygen-glucose deprivation (OGD) or glucose deprivation (GD) in primary astrocytic cultures. We show that Hsp75 overexpression decreases ROS production and preserves mitochondrial membrane potential during GD, and preserves ATP levels and cell viability during OGD. These findings indicate that Hsp75 can provide protection against ischemia-like in vitro injury and suggest that it should be further studied as a potential candidate for protection against ischemic injury.
Voloboueva
Ludmila A
LA
Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA.
Duan
Melissa
M
Ouyang
YiBing
Y
Emery
John F
JF
Stoy
Christian
C
Giffard
Rona G
RG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D000077463:Carbamide Peroxide; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004338:Drug Combinations; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010545:Peroxides / Q000494:pharmacology; D014161:Transduction, Genetic; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D004338:Drug Combinations; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D010545:Peroxides; C092306:TRAP1 protein, human; C080352:mortalin; D000077463:Carbamide Peroxide; D000255:Adenosine Triphosphate; D014508:Urea; D005947:Glucose