Cargando…
Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury
Hypothermia (HT) is a standard of care in the management of hypoxic-ischemic brain injury (HI). However, therapeutic mechanisms of HT are not well understood. We found that at the temperature of 32°C, isolated brain mitochondria exhibited significantly greater resistance to an opening of calcium-ind...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9432759/ https://www.ncbi.nlm.nih.gov/pubmed/36044480 http://dx.doi.org/10.1371/journal.pone.0273677 |
_version_ | 1784780459560927232 |
---|---|
author | Sosunov, Sergey Bhutada, Arnav Niatsetskaya, Zoya Starkov, Anatoly Ten, Vadim |
author_facet | Sosunov, Sergey Bhutada, Arnav Niatsetskaya, Zoya Starkov, Anatoly Ten, Vadim |
author_sort | Sosunov, Sergey |
collection | PubMed |
description | Hypothermia (HT) is a standard of care in the management of hypoxic-ischemic brain injury (HI). However, therapeutic mechanisms of HT are not well understood. We found that at the temperature of 32°C, isolated brain mitochondria exhibited significantly greater resistance to an opening of calcium-induced permeability transition pore (mPTP), compared to 37°C. Mitochondrial calcium buffering capacity (mCBC) was linearly and inversely dependent upon temperature (25°C—37°C). Importantly, at 37°C cyclosporine A did not increase mCBC, but significantly increased mCBC at lower temperature. Because mPTP contributes to reperfusion injury, we hypothesized that HT protects brain by improvement of mitochondrial tolerance to mPTP activation. Immediately after HI-insult, isolated brain mitochondria demonstrated very poor mCBC. At 30 minutes of reperfusion, in mice recovered under normothermia (NT) or HT, mCBC significantly improved. However, at four hours of reperfusion, only NT mice exhibited secondary decline of mCBC. HT-mice maintained their recovered mCBC and this was associated with significant neuroprotection. Direct inverted dependence of mCBC upon temperature in vitro and significantly increased mitochondrial resistance to mPTP activation after therapeutic HT ex vivo suggest that hypothermia-driven inhibition of calcium-induced mitochondrial mPTP activation mechanistically contributes to the neuroprotection associated with hypothermia. |
format | Online Article Text |
id | pubmed-9432759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-94327592022-09-01 Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury Sosunov, Sergey Bhutada, Arnav Niatsetskaya, Zoya Starkov, Anatoly Ten, Vadim PLoS One Research Article Hypothermia (HT) is a standard of care in the management of hypoxic-ischemic brain injury (HI). However, therapeutic mechanisms of HT are not well understood. We found that at the temperature of 32°C, isolated brain mitochondria exhibited significantly greater resistance to an opening of calcium-induced permeability transition pore (mPTP), compared to 37°C. Mitochondrial calcium buffering capacity (mCBC) was linearly and inversely dependent upon temperature (25°C—37°C). Importantly, at 37°C cyclosporine A did not increase mCBC, but significantly increased mCBC at lower temperature. Because mPTP contributes to reperfusion injury, we hypothesized that HT protects brain by improvement of mitochondrial tolerance to mPTP activation. Immediately after HI-insult, isolated brain mitochondria demonstrated very poor mCBC. At 30 minutes of reperfusion, in mice recovered under normothermia (NT) or HT, mCBC significantly improved. However, at four hours of reperfusion, only NT mice exhibited secondary decline of mCBC. HT-mice maintained their recovered mCBC and this was associated with significant neuroprotection. Direct inverted dependence of mCBC upon temperature in vitro and significantly increased mitochondrial resistance to mPTP activation after therapeutic HT ex vivo suggest that hypothermia-driven inhibition of calcium-induced mitochondrial mPTP activation mechanistically contributes to the neuroprotection associated with hypothermia. Public Library of Science 2022-08-31 /pmc/articles/PMC9432759/ /pubmed/36044480 http://dx.doi.org/10.1371/journal.pone.0273677 Text en © 2022 Sosunov et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sosunov, Sergey Bhutada, Arnav Niatsetskaya, Zoya Starkov, Anatoly Ten, Vadim Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury |
title | Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury |
title_full | Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury |
title_fullStr | Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury |
title_full_unstemmed | Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury |
title_short | Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury |
title_sort | mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9432759/ https://www.ncbi.nlm.nih.gov/pubmed/36044480 http://dx.doi.org/10.1371/journal.pone.0273677 |
work_keys_str_mv | AT sosunovsergey mitochondrialcalciumbufferingdependsupontemperatureandisassociatedwithhypothermicneuroprotectionagainsthypoxiaischemiainjury AT bhutadaarnav mitochondrialcalciumbufferingdependsupontemperatureandisassociatedwithhypothermicneuroprotectionagainsthypoxiaischemiainjury AT niatsetskayazoya mitochondrialcalciumbufferingdependsupontemperatureandisassociatedwithhypothermicneuroprotectionagainsthypoxiaischemiainjury AT starkovanatoly mitochondrialcalciumbufferingdependsupontemperatureandisassociatedwithhypothermicneuroprotectionagainsthypoxiaischemiainjury AT tenvadim mitochondrialcalciumbufferingdependsupontemperatureandisassociatedwithhypothermicneuroprotectionagainsthypoxiaischemiainjury |