Recombinant Fv-Hsp70 Protein Mediates Neuroprotection After Focal Cerebral Ischemia in Rats

Zhan, Xinhua; Ander, Bradley P.; Liao, Isaac; Hansen, James E.; Kim, Chester; Clements, Douglas; Weisbart, Richard H.; Nishimura, Robert N.; Sharp, Frank R.

doi:10.1161/strokeaha.109.572537

Cited by 65 publications

(63 citation statements)

References 22 publications

(24 reference statements)

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“…cDNA-encoding di-scFv was ligated into the pPICZaA yeast expression vector, and pPICZaAdi-scFv was transfected into X-33 cells. Di-scFv was expressed in and purified from X-33 supernatant using the techniques as previously described (8)(9)(10). Protein concentrations were determined by UV spectrophotometry using a NanoDrop 1000 (Thermo Fisher Scientific).…”

Section: Introductionmentioning

confidence: 99%

Optimizing a Lupus Autoantibody for Targeted Cancer Therapy

et al. 2015

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The specificity of binding by antibodies to target antigens is a compelling advantage to antibody-based cancer therapy, but most antibodies cannot penetrate cells to affect intracellular processes. Select lupus autoantibodies penetrate into cell nuclei, and the potential for application of these antibodies in cancer therapy is an emerging concept. Here, we show that a divalent lupus anti-DNA autoantibody fragment with enhancing mutations that increase its ability to penetrate cell nuclei and bind DNA causes accumulation of DNA double-strand breaks in and is highly and selectively toxic to cancer cells and tumors with defective homology-directed repair of DNA double-strand breaks. These findings provide proof of principle for the use of optimized lupus autoantibodies in targeted cancer therapy.Cancer Res; 75(11); 2285-91. Ó2015 AACR.

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Section: Introductionmentioning

confidence: 99%

Optimizing a Lupus Autoantibody for Targeted Cancer Therapy

et al. 2015

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“…The neuroprotective effect of HSP against ischemic stroke has been clearly demonstrated in transgenic mice models of HSP70 (Plumier et al 1997;Lee et al 2001;Tsuchiya et al 2003;Lee et al 2004;van der Weerd et al 2005) and HSP27 (van der Weerd et al 2010). Pharmacologic induction or intravenous administration of HSP70 also decreased the extent of infarct in rodent models of stroke (Lu et al 2002;Doeppner et al 2009;Zhan et al 2010). In addition to its role as a chaperone, the underlying neuroprotective function of HSP can also largely be explained by its anti-apoptotic properties and immune modulation (Joly et al 2010;Lanneau et al 2010).…”

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confidence: 99%

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

Lee

Jung

Lee

et al. 2017

Cell Stress and Chaperones

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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.

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“…This is demonstrated by studies showing that modified Hsp70 proteins can protect against brain ischemia when administered intravenously (Doeppner et al, 2013;Zhan et al, 2010). Besides Hsp70, upregulation of Hsp27 following stroke is also associated with a beneficial outcome.…”

Section: Protein Damps -Heat Shock Proteinsmentioning

confidence: 97%