FasL shedding is reduced by hypothermia in experimental stroke

Liping Liu, Jong Youl Kim, Maya A. Koike, Yone Jung Yoon, Xian Nan Tang, Ma Hualong, Hokyou Lee, Gary K.Steinberg, Jong Eun Lee, Midori A. Yenari

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Protection by mild hypothermia has previously been associated with better mitochondrial preservation and suppression of the intrinsic apoptotic pathway. It is also known that the brain may undergo apoptotic death via extrinsic, or receptor- mediated pathways, such as that triggered by Fas/FasL. Male Sprague-Dawley rats subjected to 2 h middle cerebral artery occlusion with 2 h intraischemic mild hypothermia (33°C) were assayed for Fas, FasL and caspase-8 expression. Ischemia increased Fas, but decreased FasL by ∼ 50-60% at 6 and 24 h post-insult. Mild hypothermia significantly reduced expression of Fas and processed caspase-8 both by ∼ 50%, but prevented ischemia-induced FasL decreases. Fractionation revealed that soluble/shed FasL (sFasL) was decreased by hypothermia, while membrane-bound FasL (mFasL) increased. To more directly assess the significance of the Fas/FasL pathway in ischemic stroke, primary neuron cultures were exposed to oxygen glucose deprivation. Since FasL is cleaved by matrix metalloproteinases (MMPs), and mild hypothermia decreases MMP expression, treatment with a pan-MMP inhibitor also decreased sFasL. Thus, mild hypothermia is associated with reduced Fas expression and caspase-8 activation. Hypothermia prevented total FasL decreases, and most of it remained membrane-bound. These findings reveal new observations regarding the effect of mild hypothermia on the Fas/FasL and MMP systems.

Original languageEnglish
Pages (from-to)541-550
Number of pages10
JournalJournal of Neurochemistry
Volume106
Issue number2
DOIs
Publication statusPublished - 2008 Jul 1

Fingerprint

Hypothermia
Stroke
Caspase 8
Matrix Metalloproteinases
Ischemia
Membranes
Matrix Metalloproteinase Inhibitors
Middle Cerebral Artery Infarction
Fractionation
Neurons
Sprague Dawley Rats
Rats
Brain
Chemical activation
Oxygen
Glucose

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Liu, L., Kim, J. Y., Koike, M. A., Yoon, Y. J., Tang, X. N., Hualong, M., ... Yenari, M. A. (2008). FasL shedding is reduced by hypothermia in experimental stroke. Journal of Neurochemistry, 106(2), 541-550. https://doi.org/10.1111/j.1471-4159.2008.05411.x
Liu, Liping ; Kim, Jong Youl ; Koike, Maya A. ; Yoon, Yone Jung ; Tang, Xian Nan ; Hualong, Ma ; Lee, Hokyou ; K.Steinberg, Gary ; Lee, Jong Eun ; Yenari, Midori A. / FasL shedding is reduced by hypothermia in experimental stroke. In: Journal of Neurochemistry. 2008 ; Vol. 106, No. 2. pp. 541-550.
@article{c1322a84af59419aad41d92bfcbbb954,
title = "FasL shedding is reduced by hypothermia in experimental stroke",
abstract = "Protection by mild hypothermia has previously been associated with better mitochondrial preservation and suppression of the intrinsic apoptotic pathway. It is also known that the brain may undergo apoptotic death via extrinsic, or receptor- mediated pathways, such as that triggered by Fas/FasL. Male Sprague-Dawley rats subjected to 2 h middle cerebral artery occlusion with 2 h intraischemic mild hypothermia (33°C) were assayed for Fas, FasL and caspase-8 expression. Ischemia increased Fas, but decreased FasL by ∼ 50-60{\%} at 6 and 24 h post-insult. Mild hypothermia significantly reduced expression of Fas and processed caspase-8 both by ∼ 50{\%}, but prevented ischemia-induced FasL decreases. Fractionation revealed that soluble/shed FasL (sFasL) was decreased by hypothermia, while membrane-bound FasL (mFasL) increased. To more directly assess the significance of the Fas/FasL pathway in ischemic stroke, primary neuron cultures were exposed to oxygen glucose deprivation. Since FasL is cleaved by matrix metalloproteinases (MMPs), and mild hypothermia decreases MMP expression, treatment with a pan-MMP inhibitor also decreased sFasL. Thus, mild hypothermia is associated with reduced Fas expression and caspase-8 activation. Hypothermia prevented total FasL decreases, and most of it remained membrane-bound. These findings reveal new observations regarding the effect of mild hypothermia on the Fas/FasL and MMP systems.",
author = "Liping Liu and Kim, {Jong Youl} and Koike, {Maya A.} and Yoon, {Yone Jung} and Tang, {Xian Nan} and Ma Hualong and Hokyou Lee and Gary K.Steinberg and Lee, {Jong Eun} and Yenari, {Midori A.}",
year = "2008",
month = "7",
day = "1",
doi = "10.1111/j.1471-4159.2008.05411.x",
language = "English",
volume = "106",
pages = "541--550",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

Liu, L, Kim, JY, Koike, MA, Yoon, YJ, Tang, XN, Hualong, M, Lee, H, K.Steinberg, G, Lee, JE & Yenari, MA 2008, 'FasL shedding is reduced by hypothermia in experimental stroke', Journal of Neurochemistry, vol. 106, no. 2, pp. 541-550. https://doi.org/10.1111/j.1471-4159.2008.05411.x

FasL shedding is reduced by hypothermia in experimental stroke. / Liu, Liping; Kim, Jong Youl; Koike, Maya A.; Yoon, Yone Jung; Tang, Xian Nan; Hualong, Ma; Lee, Hokyou; K.Steinberg, Gary; Lee, Jong Eun; Yenari, Midori A.

In: Journal of Neurochemistry, Vol. 106, No. 2, 01.07.2008, p. 541-550.

Research output: Contribution to journalArticle

TY - JOUR

T1 - FasL shedding is reduced by hypothermia in experimental stroke

AU - Liu, Liping

AU - Kim, Jong Youl

AU - Koike, Maya A.

AU - Yoon, Yone Jung

AU - Tang, Xian Nan

AU - Hualong, Ma

AU - Lee, Hokyou

AU - K.Steinberg, Gary

AU - Lee, Jong Eun

AU - Yenari, Midori A.

PY - 2008/7/1

Y1 - 2008/7/1

N2 - Protection by mild hypothermia has previously been associated with better mitochondrial preservation and suppression of the intrinsic apoptotic pathway. It is also known that the brain may undergo apoptotic death via extrinsic, or receptor- mediated pathways, such as that triggered by Fas/FasL. Male Sprague-Dawley rats subjected to 2 h middle cerebral artery occlusion with 2 h intraischemic mild hypothermia (33°C) were assayed for Fas, FasL and caspase-8 expression. Ischemia increased Fas, but decreased FasL by ∼ 50-60% at 6 and 24 h post-insult. Mild hypothermia significantly reduced expression of Fas and processed caspase-8 both by ∼ 50%, but prevented ischemia-induced FasL decreases. Fractionation revealed that soluble/shed FasL (sFasL) was decreased by hypothermia, while membrane-bound FasL (mFasL) increased. To more directly assess the significance of the Fas/FasL pathway in ischemic stroke, primary neuron cultures were exposed to oxygen glucose deprivation. Since FasL is cleaved by matrix metalloproteinases (MMPs), and mild hypothermia decreases MMP expression, treatment with a pan-MMP inhibitor also decreased sFasL. Thus, mild hypothermia is associated with reduced Fas expression and caspase-8 activation. Hypothermia prevented total FasL decreases, and most of it remained membrane-bound. These findings reveal new observations regarding the effect of mild hypothermia on the Fas/FasL and MMP systems.

AB - Protection by mild hypothermia has previously been associated with better mitochondrial preservation and suppression of the intrinsic apoptotic pathway. It is also known that the brain may undergo apoptotic death via extrinsic, or receptor- mediated pathways, such as that triggered by Fas/FasL. Male Sprague-Dawley rats subjected to 2 h middle cerebral artery occlusion with 2 h intraischemic mild hypothermia (33°C) were assayed for Fas, FasL and caspase-8 expression. Ischemia increased Fas, but decreased FasL by ∼ 50-60% at 6 and 24 h post-insult. Mild hypothermia significantly reduced expression of Fas and processed caspase-8 both by ∼ 50%, but prevented ischemia-induced FasL decreases. Fractionation revealed that soluble/shed FasL (sFasL) was decreased by hypothermia, while membrane-bound FasL (mFasL) increased. To more directly assess the significance of the Fas/FasL pathway in ischemic stroke, primary neuron cultures were exposed to oxygen glucose deprivation. Since FasL is cleaved by matrix metalloproteinases (MMPs), and mild hypothermia decreases MMP expression, treatment with a pan-MMP inhibitor also decreased sFasL. Thus, mild hypothermia is associated with reduced Fas expression and caspase-8 activation. Hypothermia prevented total FasL decreases, and most of it remained membrane-bound. These findings reveal new observations regarding the effect of mild hypothermia on the Fas/FasL and MMP systems.

UR - http://www.scopus.com/inward/record.url?scp=51649094117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51649094117&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2008.05411.x

DO - 10.1111/j.1471-4159.2008.05411.x

M3 - Article

C2 - 18410517

AN - SCOPUS:51649094117

VL - 106

SP - 541

EP - 550

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -

Liu L, Kim JY, Koike MA, Yoon YJ, Tang XN, Hualong M et al. FasL shedding is reduced by hypothermia in experimental stroke. Journal of Neurochemistry. 2008 Jul 1;106(2):541-550. https://doi.org/10.1111/j.1471-4159.2008.05411.x