Abstract
Heat shock protein A12B (HSPA12B) is the newest member of a recently defined subfamily of proteins distantly related to the 70-kDa family of heat shock proteins (HSP70) family. HSP70s play a crucial role in protecting cells, tissues, organs and animals from various noxious conditions. Here we studied the dynamic expression changes and localization of HSPA12B after middle cerebral artery occlusion (MCAO) with reperfusion induced ischemic insult processes in adult rats. Apoptosis, as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, was also increased in the peri-ischemic cortex compared to non-ischemic hemisphere. The expression of HSPA12B was strongly induced in the ischemic hemisphere of MCAO reperfusion rats in vivo. In vitro studies indicated that the up-regulation of HSPA12B may be involved in oxygen-glucose deprivation-induced PC12 cell death. And knockdown of HSPA12B in cultured differentiated PC12 cells by siRNA showed that HSPA12B inhibited the expression of active caspase-3. Collectively, these results suggested that HSPA12B may be required for protecting neurons from ischemic insults.
Similar content being viewed by others
Abbreviations
- HSPA12B:
-
Heat shock protein A12B
- MCAO:
-
Middle cerebral artery occlusion
- OGD:
-
Oxygen glucose deprivation
- CNS:
-
Central nervous system
- NGF:
-
Nerve growth factor
- NSS:
-
Neurological severity scores
- PAGE:
-
Polyacrylamide gel electrophoresis
- ECL:
-
Enhanced chemiluminescence system
- RT-PCR:
-
Reverse transcriptase PCR
- MAP2:
-
Microtubule-associated protein 2
- TUNEL:
-
Terminal deoxynucleotidyl transferase dUTP nick end labeling
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
References
Caplan LR, Schmahmann JD, Kase CS et al (1990) Caudate infarcts. Arch Neurol 47:133–143
Phipps MA (1991) Assessment of neurologic deficits in stroke. Acute-care and rehabilitation implications. Nurs Clin North Am 26:957–970
Hou SW, Wang YQ, Xu M et al (2008) Functional integration of newly generated neurons into striatum after cerebral ischemia in the adult rat brain. Stroke 39:2837–2844
Justicia C, Ramos-Cabrer P, Hoehn M (2008) MRI detection of secondary damage after stroke: chronic iron accumulation in the thalamus of the rat brain. Stroke 39:1541–1547
Fujie W, Kirino T, Tomukai N et al (1990) Progressive shrinkage of the thalamus following middle cerebral artery occlusion in rats. Stroke 21:1485–1488
Iizuka H, Sakatani K, Young W (1990) Neural damage in the rat thalamus after cortical infarcts. Stroke 21:790–794
Domercq M, Etxebarria E, Perez-Samartin A et al (2005) Excitotoxic oligodendrocyte death and axonal damage induced by glutamate transporter inhibition. Glia 52:36–46
Johnston MV (2005) Excitotoxicity in perinatal brain injury. Brain Pathol 15:234–240
Ross DT, Ebner FF (1990) Thalamic retrograde degeneration following cortical injury: an excitotoxic process? Neuroscience 35:525–550
Brown IR (2007) Heat shock proteins and protection of the nervous system. Ann N Y Acad Sci 1113:147–158
Turturici G, Sconzo G, Geraci F (2011) Hsp70 and its molecular role in nervous system diseases. Biochem Res Int 2011:618127
Parcellier A, Gurbuxani S, Schmitt E et al (2003) Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. Biochem Biophys Res Commun 304:505–512
Hoehn B, Ringer TM, Xu L et al (2001) Overexpression of HSP72 after induction of experimental stroke protects neurons from ischemic damage. J Cereb Blood Flow Metab 21:1303–1309
Batulan Z, Shinder GA, Minotti S et al (2003) High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1. J Neurosci 23:5789–5798
Marcuccilli CJ, Mathur SK, Morimoto RI et al (1996) Regulatory differences in the stress response of hippocampal neurons and glial cells after heat shock. J Neurosci 16:478–485
Tagawa K, Marubuchi S, Qi ML et al (2007) The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes. J Neurosci 27:868–880
Marinova Z, Ren M, Wendland JR et al (2009) Valproic acid induces functional heat-shock protein 70 via Class I histone deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation. J Neurochem 111:976–987
Steagall RJ, Rusinol AE, Truong QA et al (2006) HSPA12B is predominantly expressed in endothelial cells and required for angiogenesis. Arterioscler Thromb Vasc Biol 26:2012–2018
Kiang JG, Tsokos GC (1998) Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol Ther 80:183–201
Marber MS, Mestril R, Chi SH et al (1995) Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J Clin Invest 95:1446–1456
Samali A, Cotter TG (1996) Heat shock proteins increase resistance to apoptosis. Exp Cell Res 223:163–170
Takano M, Arai T, Mokuno Y et al (1998) Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-alpha-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression. Cell Stress Chaperones 3:109–117
Han Z, Truong QA, Park S et al (2003) Two Hsp70 family members expressed in atherosclerotic lesions. Proc Natl Acad Sci USA 100:1256–1261
Zhou H, Qian J, Li C et al (2011) Attenuation of cardiac dysfunction by HSPA12B in endotoxin-induced sepsis in mice through a PI3K-dependent mechanism. Cardiovasc Res 89:109–118
Cui Z, Wang P, Sun L et al (2010) Lipopolysaccharide-evoked HSPA12B expression by activation of MAPK cascade in microglial cells of the spinal cord. J Neurol Sci 294:29–37
Hillion JA, Takahashi K, Maric D et al (2005) Development of an ischemic tolerance model in a PC12 cell line. J Cereb Blood Flow Metab 25:154–162
Kritis A, Pourzitaki C, Klagas I et al (2011) Proteases inhibition assessment on PC12 and NGF treated cells after oxygen and glucose deprivation reveals a distinct role for aspartyl proteases. PLoS ONE 6:e25950
Zhang R, Zhang H, Zhang Z et al (2012) Neuroprotective effects of pre-treatment with l-carnitine and acetyl-l-carnitine on ischemic injury in vivo and in vitro. Int J Mol Sci 13:2078–2090
Chen H, Chopp M, Zhang ZG et al (1992) The effect of hypothermia on transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 12:621–628
Chen J, Li Y, Chopp M (2000) Intracerebral transplantation of bone marrow with BDNF after MCAo in rat. Neuropharmacology 39:711–716
Longa EZ, Weinstein PR, Carlson S et al (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91
Reimann-Philipp U, Ovase R, Weigel PH et al (2001) Mechanisms of cell death in primary cortical neurons and PC12 cells. J Neurosci Res 64:654–660
Genetos DC, Cheung WK, Decaris ML et al (2010) Oxygen tension modulates neurite outgrowth in PC12 cells through a mechanism involving HIF and VEGF. J Mol Neurosci 40:360–366
Chen J, Sanberg PR, Li Y et al (2001) Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 32:2682–2688
Chopp M, Li Y (1996) Apoptosis in focal cerebral ischemia. Acta Neurochir Suppl 66:21–26
Ginsberg MD (1997) The new language of cerebral ischemia. AJNR Am J Neuroradiol 18:1435–1445
Nakase T, Fushiki S, Naus CC (2003) Astrocytic gap junctions composed of connexin 43 reduce apoptotic neuronal damage in cerebral ischemia. Stroke 34:1987–1993
Wang CC, Chio CC, Chang CH et al (2010) Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia. BMC Pharmacol 10:11
Krupinski J, Ferrer I, Barrachina M et al (2002) CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology 42:846–854
Abu-Raya S, Blaugrund E, Trembovler V et al (1999) Rasagiline, a monoamine oxidase-B inhibitor, protects NGF-differentiated PC12 cells against oxygen-glucose deprivation. J Neurosci Res 58:456–463
Guo Z, Ersoz A, Butterfield DA et al (2000) Beneficial effects of dietary restriction on cerebral cortical synaptic terminals: preservation of glucose and glutamate transport and mitochondrial function after exposure to amyloid beta-peptide, iron, and 3-nitropropionic acid. J Neurochem 75:314–320
Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192:1–15
Yenari MA (2002) Heat shock proteins and neuroprotection. Adv Exp Med Biol 513:281–299
Muchowski PJ, Wacker JL (2005) Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci 6:11–22
Ren M, Senatorov VV, Chen RW et al (2003) Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model. Proc Natl Acad Sci U S A 100:6210–6215
Zheng Z, Kim JY, Ma H et al (2008) Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke. J Cereb Blood Flow Metab 28:53–63
Manzanero S, Gelderblom M, Magnus T et al (2011) Calorie restriction and stroke. Exp Transl Stroke Med 3:8
Eldadah BA, Faden AI (2000) Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma 17:811–829
Wang W, Bu B, Xie M et al (2009) Neural cell cycle dysregulation and central nervous system diseases. Prog Neurobiol 89:1–17
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 31070723 and No. 81070922); A project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Lihua Kang and Guowei Zhang contributed equally to this work.
Rights and permissions
About this article
Cite this article
Kang, L., Zhang, G., Yan, Y. et al. The Role of HSPA12B in Regulating Neuronal Apoptosis. Neurochem Res 38, 311–320 (2013). https://doi.org/10.1007/s11064-012-0922-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-012-0922-y