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Co-induction of αB-crystallin and MAPKAPK-2 in astrocytes in the penumbra after transient focal cerebral ischemia

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Abstract

αB-crystallin (α-BC), a member of the small heat-shock proteins (sHSP), is constitutively expressed in the vertebrate lens and in non-ocular tissues including the central nervous system (CNS). In this study we investigated the expression of α-BC in the rat brain after middle cerebral artery occlusion (MCAO). α-BC transcript and protein were transiently expressed 4 h after MCAO/reperfusion in the pyramidal neurons in the peri-infarct region of the ischemic hemisphere. Beginning 2 days after MCAO, significant α-BC induction appeared in reactive astrocytes in the penumbra, and this induction was sustained for several days. In addition, levels of MAPKAPK-2, one of the α-BC upstream kinases, and its phosphorylated form were upregulated gradually and peaked 4 days after ischemia/reperfusion injury. The immunohistochemical study indicated that α-BC was co-localized with MAPKAPK-2 and p-MAPKAPK-2. Furthermore, p38β MAPK, an upstream kinase of MAPKAPK-2, which has been known to be involved in compensatory responses to stress, was also co-localized with α-BC in the penumbra. Our results suggest that the p38β-dependent α-BC induction in neurons and astrocytes in the penumbra may play an important role in the postischemic brain.

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Abbreviations

α-BC:

αB-Crystalline

sHSP:

Small heat-shock protein

CNS:

Central nervous system

MCAO:

Middle cerebral artery occlusion

GFAP:

Glial fibrillary acidic protein

BBB:

Blood–brain barrier

MAPKAPK-2:

Mitogen-activated protein kinase-activated protein kinase-2

LEDGF:

Lens epithelium-derived growth factor

References

  • Armstrong SC, Shivell CL, Ganote CE (2000) Differential translocation or phosphorylation of alpha B crystallin cannot be detected in ischemically preconditioned rabbit cardiomyocytes. J Mol Cell Cardiol 32:1301–1314

    Google Scholar 

  • Ashwal S, Tone B, Tian HR, Cole DJ, Pearce WJ (1998) Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion. Stroke 29:1037–1046

    Google Scholar 

  • Bajramovic LJ, Lassmann H, Van Noort JM (1997) Expression of αB-Crystallin in glia cells during lesional development in multiple sclerosis. J Neuroimmunol 78:142–151

    Google Scholar 

  • Che Y, Piao CS, Han PL, Lee JK (2001) Delayed induction of alpha B-crystallin in activated glia cells of hippocampus in kainic acid-treated mouse brain. J Neurosci Res 65:425–431

    Google Scholar 

  • Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149

    Google Scholar 

  • Dabir DV, Trojanowski JQ, Richter-Landsberg C, Lee VM, Forman MS (2004) Expression of the small heat-shock protein alpha B-crystallin in tauopathies with glial pathology. Am J Pathol 164:155–166

    Google Scholar 

  • Feng H, Xiang H, Mao YW, Wang J, Liu JP, Huang XQ, Liu Y, Liu SJ, Luo C, Zhang XJ, Liu Y, Li DW (2004) Human Bcl-2 activates ERK signaling pathway to regulate activating protein-1, lens epithelium-derived growth factor and downstream genes. Oncogene, in press

  • Garcia JH, Yoshida Y, Chen H, Li Y, Zhang ZG, Lian HJ, Chen S, Chopp M (1993) Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am J Pathol 142:623–635

    Google Scholar 

  • Goldbaum O, Oppermann M, Handschuh M, Dabir D, Zhang B, Forman MS, Trojanowski JQ, Lee VM, Richter-Landsberg C (2003) Proteasome inhibition stabilizes tau inclusions in oligodendroglial cells that occur after treatment with okadaic acid. J Neurosci. 23:8872–8880

    Google Scholar 

  • Ha Y, Choi JU, Yoon DH, Cho YE, Kim TS (2002) Nestin and small heat-shock protein expression on reactive astrocytes and endothelial cells in cerebral abscess. Neurosci Res. 44:207–212

    Google Scholar 

  • Hoover HE, Thuerauf DJ, Martindale JJ, Glembotski CC (2000) alpha B-crystallin gene induction and phosphorylation by MKK6-activated p38. A potential role for alpha B-crystallin as a target of the p38 branch of the cardiac stress response. J Biol Chem 275:23825–23833

    Google Scholar 

  • Horwitz J (1992) Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci USA 89:10449–10453

    Google Scholar 

  • Huot J, Houle F, Spitz DR, Landry J (1996) HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. Cancer Res 56:273–279

    Google Scholar 

  • Imura T, Shimohama S, Sato M, Nishikawa H, Madono K, Akaike A, Kimura J (1999) Differential expression of small heat-shock proteins in reactive astrocytes after focal ischemia: possible role of β-adrenergic receptor. J Neurosci 19:9768–9779

    Google Scholar 

  • Iwaki T, Iwaki A, Fukumaki Y, Tateishi J (1995) Alpha B-crystallin in C6 glioma cells supports their survival in elevated extracellular K+: the implication of a protective role of alpha B-crystallin accumulation in reactive glia. Brain Res 673:47–52

    Google Scholar 

  • Iwaki T, Iwaki A, Tateishi J, Goldman JE (1994) Sense and antisense modification of glial alpha B-crystallin production results in alterations of stress fiber formation and thermoresistance. J Cell Biol 125:1385–1393

    Google Scholar 

  • Jaattela M (1999) Heat-shock proteins as cellular lifeguards. Ann Med 31:261–271

    Google Scholar 

  • Jakob U, Gaestel M, Engel K, Buchner J (1993) Small heat-shock proteins are molecular chaperones. J Biol Chem 268:1517–1520

    Google Scholar 

  • Kamradt MC, Chen F, Sam S, Cryns VL (2002) The small heat-shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation. J Biol Chem 277:38731–38736

    Google Scholar 

  • Kato H, Hofure K, Kato K (1994) Induction of 27 kDa heat-shock protein following cerebral ischemia in a rat model of ischemic tolerance. Brain Res 634:235–244

    Google Scholar 

  • Kato K, Ito H, Kamei K, Inaguma Y, Iwamoto I, Saga S (1998) Phosphorylation of alphaB-crystallin in mitotic cells and identification of enzymatic activities responsible for phosphorylation. J Biol Chem 273:28346–28354

    Google Scholar 

  • Kim JB, Piao CS, Lee KW, Han PL, Ahn JI, Lee YS, Lee JK (2004) Delayed genomic responses to transient middle cerebral artery occlusion in the rat. J Neurochem 89:1271–1282

    Google Scholar 

  • Landry J, Chretien P, Lambert H, Hickey E, Weber LA (1989) Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells. J Cell Biol 109:7–15

    Google Scholar 

  • Lang A, Schrum LW, Schoonhoven R, Tuvia S, Solis-Herruzo JA, Tsukamoto H, Brenner DA, Rippe RA (2000) Expression of small heat-shock protein alphaB-crystallin is induced after hepatic stellate cell activation. Am J Physiol Gastrointest Liver Physiol 279:G1333–G1342

    Google Scholar 

  • Lee JK, Hwang WS, Lee YD, Han PL (1999a) Dynamic expression of SEK1 suggests multiple roles of the gene during embryogenesis and in adult brain of mice. Mol Brain Res 66:133–140

    Google Scholar 

  • Lee JK, Park J, Lee YD, Lee SH, Han PL (1999b) Distinct Localization of SAPK isoforms in neurons of adult mouse brain implies multiple signaling modes of SAPK pathway. Mol Brain Res 70:116–124

    Google Scholar 

  • Li DW, Xiang H, Mao YW, Wang J, Fass U, Zhang XY, Xu C (2001) Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. Exp Cell Res 266:279–291

    Google Scholar 

  • Mao YW, Xiang H, Wang J, Korsmeyer S, Reddan J, Li DW (2001) Human bcl-2 gene attenuates the ability of rabbit lens epithelial cells against H2O2 Biol Chem 276:43435–43445

    Google Scholar 

  • Mehlen P, Kretz-Remy C, Preville X, Arrigo AP (1996) Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death. EMBO J 15:2695–2706

    Google Scholar 

  • Merck KB, Groenen PJ, Voorter CE, de Haard-Hoekman WA, Horwitz J, Bloemendal H, de Jong WW (1993) Structural and functional similarities of bovine α-Crystallin and mouse small heat-shock protein: a family of chaperones. J Biol Chem 268:1046–1052

    Google Scholar 

  • Nemoto S, Xiang J, Huang S, Lin A (1998) Induction of apoptosis by SB202190 through inhibition of p38beta mitogen-activated protein kinase. J Biol Chem 273:16415–16420

    Google Scholar 

  • Piao CS, Yu YM, Han PL, Lee JK (2003) Dynamic expression of p38beta MAPK in neurons and astrocytes after transient focal ischemia. Brain Res 976:120–124

    Google Scholar 

  • Ray PS, Martin JL, Swanson EA, Otani H, Dillmann WH, Das DK (2001) Transgene overexpression of alphaB crystallin confers simultaneous protection against cardiomyocyte apoptosis and necrosis during myocardial ischemia and reperfusion. FASEB J 15:393–402

    Google Scholar 

  • Renkawek K, Voorter CE, Bosman GJ, van Norkum FP, de Jong WW (1994) Expression of αB-Crystallin in Alzheimer’s disease. Acta Neuropathol (Berl) 87:155–160

    Google Scholar 

  • Rogalla R, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J, Gaestel M (1999) Regulation of HSP27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor-α by phosphorylation. J Biol Chem 274:18947–18956

    Google Scholar 

  • Stege GJ, Renkawek K, Overkamp PS, Verschuure P, van Rijk AF, Reijnen-Aalvers A, Boelens WC, Bosman GJ, Jong WW (1999) The molecular chaperone αB-Crystallin enhances amyloid beta neurotoxicity. Biochem Biophys Res Commun 262:152–156

    Google Scholar 

  • van Noort JM, Bajramovic LJ, Plomp AC, van Stipdonk MJ (2000) Mistaken self, a novel model that links microbial infections with myelin-directed autoimmunity in multiple sclerosis. J Neuroimmunol 105:46–57

    Google Scholar 

  • Wang Y, Huang S, Sah VP, Ross J Jr, Brown JH, Han J, Chien KR (1998) Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. J Biol Chem 273:2161–2168

    Google Scholar 

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Acknowledgement

This work was supported by a grant from the Health Planning Technology and Evaluation Board (02-PJ1-PG3–21304–0009) for J-K Lee.

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Authors and Affiliations

  1. Department of Anatomy, Inha University School of Medicine, Jung-Gu Shinheung-Dong 3rd. St. 7-241, 400-712, Inchon, Korea

    Chun-Shu Piao, Seung-Woo Kim, Jung-Bin Kim & Ja-Kyeong Lee

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  1. Chun-Shu Piao
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  2. Seung-Woo Kim
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Correspondence to Ja-Kyeong Lee.

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Piao, CS., Kim, SW., Kim, JB. et al. Co-induction of αB-crystallin and MAPKAPK-2 in astrocytes in the penumbra after transient focal cerebral ischemia. Exp Brain Res 163, 421–429 (2005). https://doi.org/10.1007/s00221-004-2197-2

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  • DOI: https://doi.org/10.1007/s00221-004-2197-2

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