αB-crystallin (α-BC), the fifth member of mammalian small heat shock protein family (HspB5), is known to be expressed in many tissues and has a distinctive interaction with cytoskeleton components. In this study, we investigated that α-BC and microtubule-associated protein-2 (MAP-2), a neuron-specific cytoskeleton protein, were coexpressed in neurons of Gerbil cortex, while in subcortex Gerbil brains, we found that several MAP-2-negative glia cells also express α-BC. When subjected to 10-minute bilateral carotid artery occlusion (BCAO), an increment was observed in α-BC-positive cells after 6-hour reperfusion and peaked at around 7 days after. In the same circumstances, the number and the staining concentration of MAP-2 positive neurons significantly decreased immediately after 6-hour reperfusion, followed by a slow recovery, which is consistent with the increase of α-BC. Our results suggested that α-BC plays an important role in brain ischemia, providing the early protection of neurons by giving intracellular supports through the maintenance of cytoskeleton and extracellular supports through the protection of glia cells. 1. Introduction αB-crystallin/HspB5 (α-BC) is one member of the mammalian small heat shock protein family which consists of ten known members from HspB1 to B10. Though isolated from the crystallin lens, it has been described in a broad number of tissues and organs including the brain, skeletal muscle, heart, and kidney, and it is shown to implicate in many diseases, such as multiple sclerosis (MS), Guillain-Barre syndrome (GBS), Alexander disease, epilepsy, Down syndrome, familial amyotrophic lateral sclerosis (FALS), familial amyloidotic polyneuropathy and chronic inflammatory demyelinating polyneuropathy [1–8]. It has been reported that α-BC functions as molecular chaperones by binding with denatured protein under stress in a reversible equilibrium state. In addition, the specific interaction between α-BC and cytoskeletal structures in cardiac and skeletal myocytes has been proved, and the interaction is enhanced after stress, which contributes to increased stress tolerance [9–12]. The increased expression of α-BC in cerebral arteriovenous malformations (AVMs) is also associated with maintenance of the intermediate fibre (IF) network, which increases wall tension caused by dilating vessels and the hemodynamic stress surrounding [13], another research found out that α-BC significantly suppressed the ADP-induced secretions of both platelet-derived growth factor (PDGF) and serotonin by inhibition of HSP27 phosphorylation via p44/p42
References
[1]
T. L. Hagemann, W. C. Boelens, E. F. Wawrousek, and A. Messing, “Suppression of GFAP toxicity by αB-crystallin in mouse models of Alexander disease,” Human Molecular Genetics, vol. 18, no. 7, pp. 1190–1199, 2009.
[2]
S. Palminiello, K. Jarzabek, K. Kaur et al., “Upregulation of phosphorylated αB-crystallin in the brain of children and young adults with Down syndrome,” Brain Research, vol. 1268, pp. 162–173, 2009.
[3]
H. Hegen, J. Wanschitz, R. Ehling et al., “Anti-αB-crystallin immunoreactivity in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy,” Journal of the Peripheral Nervous System, vol. 15, no. 2, pp. 150–152, 2010.
[4]
C. M. Karch and D. R. Borchelt, “An examination of αb-crystallin as a modifier of SOD1 aggregate pathology and toxicity in models of familial amyotrophic lateral sclerosis,” Journal of Neurochemistry, vol. 113, no. 5, pp. 1092–1100, 2010.
[5]
J. Magalh？es, S. D. Santos, and M. J. Saraiva, “αB-crystallin (HspB5) in familial amyloidotic polyneuropathy,” International Journal of Experimental Pathology, vol. 91, no. 6, pp. 515–521, 2010.
[6]
Y. K. Hayashi, “Myofibrillar myopathy,” Brain Nerve, vol. 63, no. 11, pp. 1179–1188, 2011.
[7]
J. Ojha, R. V. Karmegam, J. Gunasingh Masilamoni, A. V. Terry, and A. G. Cashikar, “Behavioral defects in chaperone-deficient Alzheimer's disease model mice,” PLoS One, vol. 6, no. 2, Article ID e16550, 2011.
[8]
J. B. Rothbard, X. Zhao, O. Sharpe et al., “Chaperone activity of α B-crystallin is responsible for its incorrect assignment as an autoantigen in multiple sclerosis,” Journal of Immunology, vol. 186, no. 7, pp. 4263–4268, 2011.
[9]
K. Djabali, B. de Nechaud, F. Landon, and M. M. Portier, “αB-crystallin interacts with intermediate filaments in response to stress,” Journal of Cell Science, vol. 110, no. 21, pp. 2759–2769, 1997.
[10]
N. Mercatelli, I. Dimauro, S. A. Ciafré, M. G. Farace, and D. Caporossi, “αB-crystallin is involved in oxidative stress protection determined by VEGF in skeletal myoblasts,” Free Radical Biology and Medicine, vol. 49, no. 3, pp. 374–382, 2010.
[11]
F. A. J. M. van de Klundert, M. L. J. Gijsen, P. R. L. A. van den Ijssel, L. H. E. H. Snoeckx, and W. W. de Jong, “αB-crystallin and hsp25 in neonatal cardiac cells—differences in cellular localization under stress conditions,” European Journal of Cell Biology, vol. 75, no. 1, pp. 38–45, 1998.
[12]
P. Verschuure, Y. Croes, P. R. L. A. van den IJssel, R. A. Quinlan, W. W. de Jong, and W. C. Boelens, “Translocation of small heat shock proteins to the actin cytoskeleton upon proteasomal inhibition,” Journal of Molecular and Cellular Cardiology, vol. 34, no. 2, pp. 117–128, 2002.
[13]
Y. Ha, T. S. Kim, D. H. Yoon, Y. E. Cho, S. G. Huh, and K. C. Lee, “Reinduced expression of developmental proteins (nestin, small heat shock protein) in and around cerebral arteriovenous malformations,” Clinical Neuropathology, vol. 22, no. 5, pp. 252–261, 2003.
[14]
Y. Enomoto, S. Adachi, R. Matsushima-Nishiwaki et al., “αB-crystallin extracellularly suppresses ADP-induced granule secretion from human platelets,” FEBS Letters, vol. 583, no. 15, pp. 2464–2468, 2009.
[15]
N. Bousette, S. Chugh, V. Fong et al., “Constitutively active calcineurin induces cardiac endoplasmic reticulum stress and protects against apoptosis that is mediated by α-crystallin-B,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 43, pp. 18481–18486, 2010.
[16]
J. H. Shin, S. W. Kim, C. M. Lim, J. Y. Jeong, C. S. Piao, and J. K. Lee, “αB-crystallin suppresses oxidative stress-induced astrocyte apoptosis by inhibiting caspase-3 activation,” Neuroscience Research, vol. 64, no. 4, pp. 355–361, 2009.
[17]
G. Watanabe, S. Kato, H. Nakata, T. Ishida, N. Ohuchi, and C. Ishioka, “αB-crystallin: a novel p53-target gene required for p53-dependent apoptosis,” Cancer Science, vol. 100, no. 12, pp. 2368–2375, 2009.
[18]
J. H. Shin, J. Y. Jeong, Y. Jin, I. D. Kim, and J. K. Lee, “P38β MAPK affords cytoprotection against oxidative stress-induced astrocyte apoptosis via induction of αB-crystallin and its anti-apoptotic function,” Neuroscience Letters, vol. 501, no. 3, pp. 132–137, 2011.
[19]
J. B. Velotta, N. Kimura, S. H. Chang et al., “αb-crystallin improves murine cardiac function and attenuates apoptosis in human endothelial cells exposed to ischemia-reperfusion,” Annals of Thoracic Surgery, vol. 91, no. 6, pp. 1907–1913, 2011.
[20]
W.-F. Hu, L. Gong, Z. Cao et al., “αA- and αB-crystallins interact with caspase-3 and bax to guard mouse lens development,” Current Molecular Medicine, vol. 12, no. 2, pp. 177–187, 2012.
[21]
S. S. Ousman, B. H. Tomooka, J. M. van Noort et al., “Protective and therapeutic role for αB-crystallin in autoimmune demyelination,” Nature, vol. 448, no. 7152, pp. 474–479, 2007.
[22]
I. J. Benjamin and D. R. McMillan, “Stress (heat shock) proteins molecular chaperones in cardiovascular biology and disease,” Circulation Research, vol. 83, no. 2, pp. 117–132, 1998.
[23]
R. C. Williams Jr., K. Sugiura, and E. M. Tan, “Antibodies to microtubule-associated protein 2 in patients with neuropsychiatric systemic lupus erythematosus,” Arthritis and Rheumatism, vol. 50, no. 4, pp. 1239–1247, 2004.
[24]
C. Sánchez, J. Díaz-Nido, and J. Avila, “Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function,” Progress in Neurobiology, vol. 61, no. 2, pp. 133–168, 2000.
[25]
Y. Fujita, E. Ohto, E. Katayama, and Y. Atomi, “αB-Crystallin-coated MAP microtubule resists nocodazole and calcium-induced disassembly,” Journal of Cell Science, vol. 117, no. 9, pp. 1719–1726, 2004.
[26]
Z. Hu, L. Zeng, L. Xie et al., “Morphological alteration of Golgi apparatus and subcellular compartmentalization of TGF-β1 in Golgi apparatus in gerbils following transient forebrain ischemia,” Neurochemical Research, vol. 32, no. 11, pp. 1927–1931, 2007.
[27]
P. R. L. A. van den Ijssela, P. Overkampa, U. Knaufb, M. Gaestelb, and W. W. de Jong, “αA-crystallin confers cellular thermoresistance,” FEBS Letters, vol. 355, no. 1, pp. 54–56, 1994.
[28]
P. J. Muchowski and J. L. Wacker, “Modulation of neurodegeneration by molecular chaperones,” Nature Reviews Neuroscience, vol. 6, no. 1, pp. 11–22, 2005.
[29]
S. Narayanan, B. Kamps, W. C. Boelens, and B. Reif, “αB-crystallin competes with Alzheimer's disease β-amyloid peptide for peptide-peptide interactions and induces oxidation of Abeta-Met35,” FEBS Letters, vol. 580, no. 25, pp. 5941–5946, 2006.
[30]
J. J. Bajramovic, A. C. Plomp, A. Goes, et al., “Presentation of alpha B-crystallin to T cells in active multiple sclerosis lesions: an early event following inflammatory demyelination,” The Journal of Immunology, vol. 164, no. 8, pp. 4359–4366, 2000.
[31]
C. S. Piao, S. W. Kim, J. B. Kim, and J. K. Lee, “Co-induction of αB-crystallin and MAPKAPK-2 in astrocytes in the penumbra after transient focal cerebral ischemia,” Experimental Brain Research, vol. 163, no. 4, pp. 421–429, 2005.
[32]
Z. Hu and T. Li, “HspB5/αB-crystallin: properties and current progress in neuropathy,” Current Neurovascular Research, vol. 5, no. 2, pp. 143–152, 2008.
[33]
F. Bennardini, A. Wrzosek, and M. Chiesi, “αB-Crystallin in cardiac tissue: association with actin and desmin filaments,” Circulation Research, vol. 71, no. 2, pp. 288–294, 1992.
[34]
R. B. Maccioni and V. Cambiazo, “Role of microtubule-associated proteins in the control of microtubule assembly,” Physiological Reviews, vol. 75, no. 4, pp. 835–864, 1995.
[35]
D. F. Matesic and R. C. S. Lin, “Microtubule-associated protein 2 as an early indicator of ischemia- induced neurodegeneration in the gerbil forebrain,” Journal of Neurochemistry, vol. 63, no. 3, pp. 1012–1020, 1994.
[36]
D. A. Dawson and J. M. Hallenbeck, “Acute focal ischemia-induced alterations in MAP2 immunostaining: description of temporal changes and utilization as a marker for volumetric assessment of acute brain injury,” Journal of Cerebral Blood Flow and Metabolism, vol. 16, no. 1, pp. 170–174, 1996.
[37]
S. M. de Waegh, V. M. Y. Lee, and S. T. Brady, “Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells,” Cell, vol. 68, no. 3, pp. 451–463, 1992.
[38]
S. T. Hsieh, G. J. Kidd, T. O. Crawford et al., “Regional modulation of neurofilament organization by myelination in normal axons,” Journal of Neuroscience, vol. 14, no. 11, pp. 6392–6401, 1994.
[39]
J. M. Edgar, M. McLaughlin, D. Yool et al., “Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia,” Journal of Cell Biology, vol. 166, no. 1, pp. 121–131, 2004.
[40]
R. Whittaker, M. S. Glassy, N. Gude, M. A. Sussman, R. A. Gottlieb, and C. C. Glembotski, “Kinetics of the translocation and phosphorylation of αB-crystallin in mouse heart mitochondria during ex vivo ischemia,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 296, no. 5, pp. H1633–H1642, 2009.
