HSP70-mediated neuroprotection by combined treatment of valproic acid with hypothermia in a rat asphyxial cardiac arrest model
| Autor: | Se-min Choi, Hyun Ho Jeong, Jungtaek Park, Kyoung Ho Choi, Joo Suk Oh, Kiwook Kim, Young Min Oh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Hypothermia Pharmacology Biochemistry Hippocampus Heat Shock Response Rats Sprague-Dawley Histones Hypothermia Induced Medicine and Health Sciences Cardiac Arrest Medicine Hsp70 mrna Cellular Stress Responses Valproic Acid Multidisciplinary Drugs Brain Acetylation Combined Modality Therapy Neuroprotection Cell Processes Epigenetics lipids (amino acids peptides and proteins) medicine.symptom Anatomy medicine.drug Research Article Science Cardiology Return of spontaneous circulation Histone H3 Asphyxia Combined treatment Signs and Symptoms DNA-binding proteins Genetics Animals HSP70 Heat-Shock Proteins Biology and life sciences business.industry Proteins Cell Biology Hsp70 Heart Arrest Rats Disease Models Animal Clinical Medicine business Neuroprotectives |
| Zdroj: | PLoS ONE, Vol 16, Iss 6, p e0253328 (2021) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | It has been reported that valproic acid (VPA) combined with therapeutic hypothermia can improve survival and neurologic outcomes in a rat asphyxial cardiac arrest model. However, neuroprotective mechanisms of such combined treatment of valproic acid with hypothermia remains unclear. We hypothesized that epigenetic regulation of HSP70 by histone acetylation could increase HSP70-mediated neuroprotection suppressed under hypothermia. Male Sprague-Dawley rats that achieved return of spontaneous circulation (ROSC) from asphyxial cardiac arrest were randomized to four groups: normothermia (37°C ± 1°C), hypothermia (33°C ± 1°C), normothermia + VPA (300 mg/kg IV initiated 5 minutes post-ROSC and infused over 20 min), and hypothermia + VPA. Three hours after ROSC, acetyl-histone H3 was highly expressed in VPA-administered groups (normothermia + VPA, hypothermia + VPA). Four hours after ROSC, HSP70 mRNA expression levels were significantly higher in normothermic groups (normothermia, normothermia + VPA) than in hypothermic groups (hypothermia, hypothermia + VPA). The hypothermia + VPA group showed significantly higher HSP70 mRNA expression than the hypothermia group. Similarly, at five hours after ROSC, HSP70 protein levels were significantly higher in normothermic groups than in hypothermic groups. HSP70 levels were significantly higher in the hypothermia + VPA group than in the hypothermia group. Only the hypothermia + VPA group showed significantly attenuated cleaved caspase-9 levels than the normothermia group. Hypothermia can attenuate the expression of HSP70 at transcriptional level. However, VPA administration can induce hyperacetylation of histone H3, leading to epigenetic transcriptional activation of HSP70 even in a hypothermic status. Combining VPA treatment with hypothermia may compensate for reduced activation of HSP70-mediated anti-apoptotic pathway. |
| Databáze: | OpenAIRE |
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