Heat Shock Protein hsp72 Induction in Cortical and Striatal Astrocytes and Neurons following Infarction

Jung

Cell Stress and Chaperones

et al. 2017

Hypothermia (HT) is a well-established neuroprotective strategy against neonatal hypoxic ischemic encephalopathy (HIE). The overexpression of heat shock proteins (HSP) has been shown to provide neuroprotection in animal models of stroke. We aimed to investigate the effect of HT on HSP70 and HSP27 expression in a neonatal rat model of HIE. Seven-day-old rat pups were exposed to hypoxia for 90 min to establish the Rice-Vannucci model and were assigned to the following four groups: hypoxic injury (HI)-normothermia (NT, 36°C), HI-HT (30°C), sham-NT, and sham-HT. After temperature intervention for 24 h, the mRNA and protein expression of HSP70 and HSP27 were measured. The association between HSP expression and brain injury severity was also evaluated. The brain infarct size was significantly smaller in the HI-HT group than in the HI-NT group. The mRNA and protein expression of both HSPs were significantly greater in the two HI groups, compared to those in the two sham groups. Moreover, among the rat pups subjected to HI, HT significantly reduced the mRNA and protein expression of both HSPs. The mRNA expression level of the HSPs was proportional to the brain injury severity. Post-ischemic HT, i.e., a cold shock attenuated the expression of HSP70 and HSP27 in a neonatal rat model of HIE. Our study suggests that neither HSP70 nor HSP27 expression is involved in the neuroprotective mechanism through which prolonged HT protects against neonatal HIE.

Section: Discussionmentioning

confidence: 99%

Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy

Jung

Cell Stress and Chaperones

et al. 2017

J Cereb Blood Flow Metab

“…Studies have shown that levels of mitochondrial Hsp70 (Hsp75) and cytosolic inducible Hsp70 (Hsp72) are upregulated during ischemic conditions (Kiang and Tsokos, 1998;Sharp et al, 1991). It has been shown that Hsp72 overexpression is neuroprotective both in vitro and in vivo (reviewed in Giffard and Yenari, 2004), inhibits early mitochondrial cytochrome c release after permanent focal ischemia Figure 3 Hsp75 overexpression preserves mitochondrial membrane potential during glucose deprivation (GD).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Mitochondrial Hsp70/Hsp75 Protects Astrocytes against Ischemic Injury in vitro

Voloboueva

Duan

Ouyang

et al. 2007

107

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.

J Cereb Blood Flow Metab

“…Sim ilarly, Simon et al (1991) found that short durations of global ischemia induced HSP70 in neurons that did not die, as assessed by acid fuchsin stains. Sharp et al (1991a) also found that MK-801, phen cyclidine, and ketamine induce HSP70 in cingulate gyrus neurons, which are known to survive. Our transient focal cerebral ischemic data show that HSP70 is induced in neurons throughout cortex fol lowing 30-min MCA occlusions and in neurons in penumbral (border) areas of the cortical ischemic lesion in 60-and 90-min MCA occlusion groups, where there is no evidence of infarction at that time point.…”

Section: This Induction In the Endothelial Cells In Infarcted Brain Rmentioning

confidence: 99%

Induction of 70-kDa Heat Shock Protein and hsp70 mRNA following Transient Focal Cerebral Ischemia in the Rat

Kinouchi

Sharp

Hill

et al. 1993

Self Cite

185

Summary: Induction of the 70-kDa heat shock protein (HSP70) was demonstrated immunocytochemically in adult rats 4 h to 7 days following temporary middle cere bral artery (MeA) occlusions lasting 30, 60, or 90 min. Maximal HSP70 induction occurred �24 h following ischemia. Thirty minutes of ischemia induced HSP70 in neurons throughout the cortex in the MeA distribution, whereas 90 min of ischemia induced HSP70 in neurons in the penumbra. HSP70 protein was induced in endothelial cells in infarcted neocortex following 60-90 min of MeA occlusion, and HSP70 was induced in endothelial cells in infarcted regions of lateral striatum following 30-90 min Normal rat brain cells do not express the 70-kDa heat shock protein (HSP70) (Vass et aI. , 1988; Brown et aI. , 1989; Gonzalez et aI. , 1989; Sharp et aI. , 1991a,b), which is a product of the hsp70 gene (Hunt and Morimoto, 1985). HSP70 is induced in brain in response to hyperthermia (Brown, 1983;Sprang and Brown, 1987; Barbe et aI. , 1988), epi lepsy (Gonzalez et aI. , 1989; Vass et aI. , 1989; Lo wenstein et aI., 1990), hypoxia-ischemia (Nowak, 1985 Kiessling et aI. , 1986; Vass et aI. , 1988; Dwy er et aI. , 1989; Gonzalez et aI., 1989; Ferriero et aI. , 1990), injection of excitotoxins (Uney et aI. , 1988; Gonzalez et aI. , 1989) 105of MeA occlusion. hsp70 mRNA was induced in the MeA distribution in cortex and to a lesser extent in stri atum at 2 h to 3 days following 60 min of ischemia. It is proposed that brief ischemia induces hsp70 mRNA and HSP70 protein in the cells most vulnerable to ischemia the neurons. HSP70 protein is not induced in most neu rons and glia following 60-90 min of ischemia in areas destined to infarct, whereas it is induced in vascular en dothelial cells. Key Words: Focal brain-hsp70 mRNA Middle cerebral artery-Stress and heat shock protein Stroke.1981; Brown et aI. , 1989). Gonzalez et al. (1989) emphasized the potential value of using HSP70 im munostaining as a sensitive marker of brain cell in jury.HSPs are a family of proteins that perform many functions. Some 60-to 80-kDa HSPs appear to chaperone protein movements across membranes and mediate important protein-protein interactions in normal and stressed cells (Chapell et aI. , 1986;Ellis, 1987; Chirico et aI. , 1988; Cheng et aI. , 1989; Chiang et aI. , 1989; Deshaies et aI. , 1989; Beck mann et aI. , 1990). Some 90-kDa HSPs regulate ste roid receptor availability.Once HSPs are induced, they may prevent pro teins from being denatured (Pelham, 1986) and pro tect cells from subsequent injury (Schlesinger et aI. , 1982;Johnston and Kucey, 1988; Riabowol et aI., 1988). Barbe et al. (1988) provided the first direct evidence for this protective role in the CNS by showing that preinduction in the rabbit retina via systemic hyperthermia is associated with a de crease in light-induced retinal injury. Moreover, mild global cerebral ischemia, sufficient to induce 106 H. KINOUCHI ET AL.HSP70 in the hippocampus, attenuates the hippo campal injury associated with a subsequent severe ischemic...