Recombinant human Tat-Hsp70-2: A tool for neuroprotection

Cappelletti, Pamela; Binda, Elisa; Tunesi, Marta; Albani, Diego; Giordano, Carmen; Molla, Gianluca; Pollegioni, Loredano

doi:10.1016/j.pep.2016.07.005

Cited by 10 publications

(6 citation statements)

References 31 publications

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“…C). The ability of pLG72 to hydrolyze GTP was assessed by assaying the amount of phosphate released from 1 m m GTP after 60 min of incubation at 37 °C . For all variants, the absorbance intensity at 660 nm could not be distinguished from the control performed in the absence of pLG72.…”

Section: Resultsmentioning

confidence: 99%

“…An equal volume of a solution containing 1% (w/v) ammonium molybdate, 6% (w/v) ascorbic acid, 2% (w/v) sodium citrate, and 2% (v/v) acetic acid was added to the assay mixture, followed by incubation at 45 °C for 25 min. The release of inorganic phosphate was quantified by measuring absorbance at 660 nm . ATPase/GTPase activity is reported as amount of released phosphate.…”

Section: Methodsmentioning

confidence: 99%

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Elucidating the role of the pLG72 R30K substitution in schizophrenia susceptibility

et al. 2017

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In the human brain, pLG72 interacts with the flavoenzyme d-amino acid oxidase (hDAAO), which is involved in catabolism of d-serine, a co-agonist of N-methyl-d-aspartate receptors (NMDAR). Here, we investigated the wild-type pLG72, the R30K variant associated with schizophrenia susceptibility, and the K62E variant. The protein conformation, oligomeric state, ligand-, and hDAAO-binding properties are only slightly modified by the substitutions. All pLG72 variants inhibit hDAAO and lead to an increase in cellular (d/d+l)-serine. However, the R30K pLG72 is significantly more prone to degradation than the R30 and the K62E variants in a cell system, thus possessing a lower ability to interact/inhibit hDAAO. This links R30K pLG72 with the hyperactivity of hDAAO, the decreased d-serine level, and NMDAR hypofunction observed in schizophrenia-affected patients.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Elucidating the role of the pLG72 R30K substitution in schizophrenia susceptibility

et al. 2017

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“…The recombinant protein, TAT-Hsp70 has shown efficacy in several pathological conditions including hypoxia-ischemia (Doeppner et al 2009; Lai et al 2005; Doeppner et al 2013; Doeppner et al 2012), Parkinson’ s disease models (Nagel et al 2008), spinal cord ischemic injury (Kim et al 2019), lung injury (Lyons et al 2015), neuronal differentiation (Kwon et al 2019). Another TAT-Hsp70-2 protein was also produced with reported neuroprotective properties (Cappellett 2017).…”

Section: Discussionmentioning

confidence: 99%

Cellular protection from H₂O₂toxicity by Fv-Hsp70. Protection via catalase and gamma-glutamyl cysteine synthase

Hino

Chan

Jordaan

et al. 2023

Preprint

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Heat shock proteins (HSPs), especially Hsp70 (HSPA1), have been associated with cellular protection from various cellular stresses including heat, hypoxia-ischemia, neurodegeneration, toxins, and trauma. Endogenous HSPs are often synthesized in direct response to these stresses but in many situations are inadequate in protecting cells. The present study addresses the transduction of Hsp70 into cells providing protection from acute oxidative stress by H2O2. The recombinant Fv-Hsp70 protein and two mutant Fv-Hsp70 proteins minus the ATPase domain, and minus the ATPase and terminal lid domains were tested at 0.5 and 1.0 uM concentrations after two different concentrations of H2O2 treatment. All three recombinant proteins protected SH-SY5Y cells from acute H2O2 toxicity. This data indicated that the protein binding domain was responsible for cellular protection. In addition, experiments pretreating cells with inhibitors of antioxidant proteins catalase and gamma-glutamylcysteine synthase (GGCS) before H2O2 resulted in cell death despite treatment with Fv-Hsp70, implying that both enzymes were protected from acute oxidative stress after treatment with Fv-Hsp70. This study demonstrates that Fv-Hsp70 is protective in our experiments primarily by the protein-binding domain. The Hsp70 terminal lid domain was also not necessary for protection. Cellular protection was protective via the antioxidant proteins catalase and GGCS.

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“…This has been proven by genetic mutation models. 13,14 HSP 70 presents in the brain under normal physiological conditions, but after 10 minutes of ischemic events, the value will increase for the next 24 hours. It can increase last up to day 7.…”

Section: Discussionmentioning

confidence: 99%

Blood Pressure and Heat Shock Protein 70 Levels Related to Acute Ischemic Stroke Severity

Indra¹,

Khair²,

Trisna³

2020

GMJ

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Introduction: Hypertension is a risk factor of ischemic stroke, the prevalence of ischemic stroke in Indonesia is 34.1%. Heat Shock Protein (HSP) 70 increases in hypertension and acute phase of ischemic stroke. To determine differences of blood pressure (BP) and HSP 70 levels, related to the acute ischemic stroke severity. Methods: This was a cross-sectional study that was carried out in the Neurological Ward of Dr.M.Djamil Hospital and National Stroke Hospital, from May to September 2019. Inclusion criteria were obtained consecutively. BP was measured with a sphygmomanometer, stroke severity was measured by NIHSS, and HSP 70 levels was analyzed by the ELISA. Computerized statistical analyzes were performed using SPSS software version 23.0 for windows. The result was statistically significant if the p-value < 0.05. Results: There were 40 samples consisted of 26 (65%) male, mean age 59.78 years. The systolic BP ranging from 130 to 190 mmHg (median 160), the diastolic BP ranging from 70 to 100 mmHg (median 90), the HSP 70 levels ranging from 2.50 to 19.56 ng/mL (median 2.72). There were 18 patients with mild stroke and 22 patients with moderate stroke. There was no significant difference between systolic blood pressure (SBP), diastolic blood pressure (DBP), and severity of stroke (p=0,369; p=0,221, respectively). There was no significant difference between HSP 70 levels and the severity of stroke (p=0,312). There was no relation between the degree of BP and HSP 70 levels. Conclusion: There were no significant differences of SBP, DBP, and HSP 70 with the acute ischemic stroke severity.

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Recombinant human Tat-Hsp70-2: A tool for neuroprotection

Cited by 10 publications

References 31 publications

Elucidating the role of the pLG72 R30K substitution in schizophrenia susceptibility

Elucidating the role of the pLG72 R30K substitution in schizophrenia susceptibility

Cellular protection from H₂O₂toxicity by Fv-Hsp70. Protection via catalase and gamma-glutamyl cysteine synthase

Blood Pressure and Heat Shock Protein 70 Levels Related to Acute Ischemic Stroke Severity

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Recombinant human Tat-Hsp70-2: A tool for neuroprotection

Cited by 10 publications

References 31 publications

Elucidating the role of the pLG72 R30K substitution in schizophrenia susceptibility

Elucidating the role of the pLG72 R30K substitution in schizophrenia susceptibility

Cellular protection from H2O2toxicity by Fv-Hsp70. Protection via catalase and gamma-glutamyl cysteine synthase

Blood Pressure and Heat Shock Protein 70 Levels Related to Acute Ischemic Stroke Severity

Contact Info

Product

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Cellular protection from H₂O₂toxicity by Fv-Hsp70. Protection via catalase and gamma-glutamyl cysteine synthase