Heme oxygenase-1 aggravates heat stress-induced neuronal injury and decreases autophagy in cerebellar Purkinje cells of rats
| Autor: | Tsung Ta Liu, Jia Yi Wang, Chuan Wang Li, Yuh Feng Lin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Time Factors Purkinje cell Down-Regulation Apoptosis Cell Count Caspase 3 medicine.disease_cause Hippocampus General Biochemistry Genetics and Molecular Biology Body Temperature Rats Sprague-Dawley Purkinje Cells Autophagy medicine Animals Cell damage Dehydration Chemistry Neurodegeneration Deoxyguanosine Hyperthermia Induced medicine.disease Molecular biology Rats Heme oxygenase Oxidative Stress medicine.anatomical_structure Biochemistry 8-Hydroxy-2'-Deoxyguanosine Nerve Degeneration Beclin-1 Apoptosis Regulatory Proteins Microtubule-Associated Proteins Heat-Shock Response Heme Oxygenase-1 Oxidative stress |
| Zdroj: | Experimental Biology and Medicine. 238:744-754 |
| ISSN: | 1535-3699 1535-3702 |
| DOI: | 10.1177/1535370213493705 |
| Popis: | We previously reported that heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain. Heme oxygenase (HO)-1 is a stress protein and can be induced by heat stress (HS). Cerebellar Purkinje cells are selectively vulnerable to heat-induced injury. In this study, we first validated an animal model of HS (38℃ for 4 h) in which sustained increase of Purkinje cell injury, HO-1 expression up to 24 h post HS (HS24), and hyperthermia reaching a rectal temperature 41.52 ± 0.32℃ were observed. In subsequent experiments, we investigated the effects of HO-1 on HS-induced Purkinje cell injury. Rats were divided into four groups: one normothermic control group receiving saline vehicle (1 mL/kg, intraperitoneal [i.p.]) and exposed to 25℃ for 4 h; and three HS groups receiving saline, or HO-1 inducer haemin (30 mg/kg, i.p.) or HO-1 inhibitor tin protoporphyrin (SnPP, 30 mg/kg, i.p.), respectively, at 12 h prior to HS. HS-induced Purkinje cell injury was further enhanced by HO-1 inducer but attenuated by HO-1 inhibitor as evaluated by immunoreactivity of apoptosis marker (active caspase-3) as well as Fluoro-Jade B histochemistry (staining for degenerating neurons), suggesting a detrimental role of HO-1. Interestingly, the protective autophagy was reduced by HO-1 inducer but enhanced by HO-1 inhibitor as demonstrated by autophagy markers including Beclin-1 and microtubule-associated protein light chain 3 in Purkinje cells. Double immunofluorescent labelling of Beclin-1 or 8-hydroxydeoxyguanosine (an oxidative DNA damage marker) with HO-1 immunoreactivity not only demonstrated their co-localization, but also confirmed that HO-1 negatively regulated Beclin-1 but increased oxidative stress in the same Purkinje cell. Taken together, our results indicate that HO-1 aggravates HS injury in cerebellar Purkinje cells. Our findings shed new light on cell damage mechanisms by HS in central nervous system and may help to provide potential therapeutic foci. |
| Databáze: | OpenAIRE |
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