Dynamic changes in proprotein convertase 2 activity in cortical neurons after ischemia/reperfusion and oxygen-glucose deprivation

doi:10.3969/j.issn.1673-5374.2013.01.011

Abstract

Abstract:

In this study, a rat model of transient focal cerebral ischemia was established by performing 100 minutes of middle cerebral artery occlusion, and an in vitro model of experimental oxygen-glucose deprivation using cultured rat cortical neurons was established. Proprotein convertase 2 activity gradually decreased in the ischemic cortex with increasing duration of reperfusion. In cultured rat cortical neurons, the number of terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate-biotin nick end labeling-positive neurons significantly increased and proprotein convertase 2 activity also decreased gradually with increasing duration of oxygen-glucose deprivation. These experimental findings indicate that proprotein convertase 2 activity decreases in ischemic rat cortex after reperfusion, as well as in cultured rat cortical neurons after oxygen-glucose deprivation. These changes in enzyme activity may play an important pathological role in brain injury.

Key words: neural regeneration, brain injury, proprotein convertase 2, cortex, neuron, cerebral ischemia/reperfusion, oxygen-glucose deprivation, in vivo study, in vitro study, grants-supported paper, photographs-containing paper, neuroregeneration

Shuqin Zhan, An Zhou, Chelsea Piper, Tao Yang. Dynamic changes in proprotein convertase 2 activity in cortical neurons after ischemia/reperfusion and oxygen-glucose deprivation[J]. Neural Regeneration Research, 2013, 8(1): 83-89.

References

1. Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev. 2007;54(1):34-66. http://www.sciencedirect.com/science/article/pii/S0165017306001172

2. Hayashi T, Abe K. Ischemic neuronal cell death and organellae damage. Neurol Res. 2004;26(8):827-834.http://www.jci.org/articles/view/16993

3.Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22(9):391-397.http://www.sciencedirect.com/science/journal/01662236

4.Nedergaard M, Kraig RP, Tanabe J, et al. Dynamics of interstitial and intracellular pH in evolving brain infarct. Am J Physiol. 1991;260(3 Pt 2):R581-588.http://ajpregu.physiology.org/content/260/3/R581.reprint

5. Paschen W, Doutheil J. Disturbances of the functioning of endoplasmic reticulum: a key mechanism underlying neuronal cell injury? J Cereb Blood Flow Metab. 1999;19(1):1-18.http://www.nature.com/jcbfm/journal/v19/n1/full/9590492a.html

6. Zhou A, Webb G, Zhu X, et al. Proteolytic processing in the secretory pathway. J Biol Chem. 1999;274(30):20745-20748.http://www.jbc.org/content/274/30/20745.long

7. Friedman TC, Loh YP, Birch NP. In vitro processing of proopiomelanocortin by recombinant PC1 (SPC3). Endocrinology. 1994;135(3):854-862.http://endo.endojournals.org/content/135/3/854.long

8. Friedman TC, Loh YP, Cawley NX, et al. Processing of prothyrotropin-releasing hormone (Pro-TRH) by bovine intermediate lobe secretory vesicle membrane PC1 and PC2 enzymes. Endocrinology. 1995;136(10):4462-4472.http://endo.endojournals.org/content/136/10/4462.long

9. Bloomquist BT, Eipper BA, Mains RE. Prohormone-converting enzymes: regulation and evaluation of function using antisense RNA. Mol Endocrinol. 1991;5(12):2014-2024.http://mend.endojournals.org/content/5/12/2014.long

10. Galanopoulou AS, Kent G, Rabbani SN, et al. Heterologous processing of prosomatostatin in constitutive and regulated secretory pathways. Putative role of the endoproteases furin, PC1, and PC2. J Biol Chem. 1993;268(8):6041-6049.http://www.jbc.org/content/268/8/6041.long

11. Perone MJ, Ahmed I, Linton EA, et al. Procorticotrophin releasing hormone is endoproteolytically processed by the prohormone convertase PC2 but not by PC1 within stably transfected CHO-K1 cells. Biochem Soc Trans. 1996;24(3):497S.http://www.biochemsoctrans.org/bst/default.htm

12. Johanning K, Mathis JP, Lindberg I. Role of PC2 in proenkephalin processing: antisense and overexpression studies. J Neurochem. 1996;66(3):898-907.http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.1996.66030898.x/abstract

13.Zhan S, Zhao H, J White A, et al. Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains. J Cereb Blood Flow Metab. 2009;29(4):698-706. http://www.nature.com/jcbfm/journal/v29/n4/full/jcbfm2008161a.html

14. Ni XP, Pearce D, Butler AA, et al. Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest. 2003;111(8):1251-1258.http://www.jci.org/articles/view/16993

15. Yan SF, Fujita T, Lu J, et al. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat Med. 2000;6(12):1355-1361.http://www.nature.com/doifinder/10.1038/82168

16. Rouillé Y, Duguay SJ, Lund K, et al. Proteolytic processing mechanisms in the biosynthesis of neuroendocrine peptides: the subtilisin-like proprotein convertases. Front Neuroendocrinol. 1995;16(4):322-361.http://www.sciencedirect.com/science/article/pii/S0091302285710126

17. Seidah NG, Chrétien M. Eukaryotic protein processing: endoproteolysis of precursor proteins. Curr Opin Biotechnol. 1997;8(5):602-607.http://www.sciencedirect.com/science/article/pii/S0958166997800365

18. Muller L, Lindberg I. The cell biology of the prohormone convertases PC1 and PC2. Prog Nucleic Acid Res Mol Biol. 1999;63:69-108.http://www.ncbi.nlm.nih.gov/pubmed/10506829

19. Seidah NG, Gaspar L, Mion P, et al. cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases. DNA Cell Biol. 1990;9(6):415-424.http://www.ncbi.nlm.nih.gov/pubmed/2169760

20. Seidah NG, Marcinkiewicz M, Benjannet S, et al. Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2. Mol Endocrinol. 1991;5(1):111-122.http://mend.endojournals.org/content/5/1/111.long

21. Seidah NG. What lies ahead for the proprotein convertases? Ann N Y Acad Sci. 2011;1220:149-161. http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05883.x/abstract;jsessionid=EFAB84F3384C08126F7AA03473C695CE.d03t03

22. Li QL, Naqvi S, Shen X, et al. Prohormone convertase 2 enzymatic activity and its regulation in neuro-endocrine cells and tissues. Regul Pept. 2003;110(3):197-205.http://www.sciencedirect.com/science/article/pii/S0167011502002070

23. Seidah NG. The proprotein convertases, 20 years later. Methods Mol Biol. 2011;768:23-57.http://www.springerlink.com/content/g893735t6225445j/#section=933726&page=1

24. Croissandeau G, Wahnon F, Yashpal K, et al. Increased stress-induced analgesia in mice lacking the proneuropeptide convertase PC2. Neurosci Lett. 2006;406(1-2):71-75. http://www.sciencedirect.com/science/article/pii/S030439400600677X

25. Mbikay M, Seidah NG, Chrétien M. Neuroendocrine secretory protein 7B2: structure, expression and functions. Biochem J. 2001;357(Pt 2):329-342.http://www.biochemj.org/bj/357/0329/bj3570329.htm

26. Lamango NS, Zhu X, Lindberg I. Purification and enzymatic characterization of recombinant prohormone convertase 2: stabilization of activity by 21 kDa 7B2. Arch Biochem Biophys. 1996;330(2):238-250.http://www.sciencedirect.com/science/article/pii/S0003986196902490

27. Shen FS, Seidah NG, Lindberg I. Biosynthesis of the prohormone convertase PC2 in Chinese hamster ovary cells and in rat insulinoma cells. J Biol Chem. 1993;268(33):24910-24915.http://www.jbc.org/content/268/33/24910.long

28. Mbikay M, Seidah NG, Chrétien M. Neuroendocrine secretory protein 7B2: structure, expression and functions. Biochem J. 2001;357(Pt 2):329-342.http://www.biochemj.org/bj/357/0329/bj3570329.htm

29. Fortenberry Y, Liu J, Lindberg I. The role of the 7B2 CT peptide in the inhibition of prohormone convertase 2 in endocrine cell lines. J Neurochem. 1999;73(3):994-1003.http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.1999.0730994.x/abstract

30. Furuta M, Yano H, Zhou A, et al. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc Natl Acad Sci U S A. 1997;94(13):6646-6651.http://www.pnas.org/content/94/13/6646.long

31. Zhang X, Pan H, Peng B, et al. Neuropeptidomic analysis establishes a major role for prohormone convertase-2 in neuropeptide biosynthesis. J Neurochem. 2010;112(5):1168-1179. http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2009.06530.x/abstract;jsessionid=B8A27310C1B9A3437EF4A3D16DFE4570.d03t01

32. Zhou A, Minami M, Zhu X, et al. Altered biosynthesis of neuropeptide processing enzyme carboxypeptidase E after brain ischemia: molecular mechanism and implication. J Cereb Blood Flow Metab. 2004;24(6):612-622.http://www.nature.com/jcbfm/journal/v24/n6/full/9591563a.html

33. Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84-91.http://stroke.ahajournals.org/content/20/1/84.long

34. Shimizu S, Nagayama T, Jin KL, et al. bcl-2 Antisense treatment prevents induction of tolerance to focal ischemia in the rat brain. J Cereb Blood Flow Metab. 2001;21(3):233-243.http://www.nature.com/jcbfm/journal/v21/n3/full/9591059a.html

35. Memezawa H, Minamisawa H, Smith ML, et al. Ischemic penumbra in a model of reversible middle cerebral artery occlusion in the rat. Exp Brain Res. 1992;89(1):67-78.http://www.ncbi.nlm.nih.gov/pubmed/1601103

36. Shimizu S, Simon RP, Graham SH. Dimethylsulfoxide (DMSO) treatment reduces infarction volume after permanent focal cerebral ischemia in rats. Neurosci Lett. 1997;239(2-3):125-127.http://www.sciencedirect.com/science/article/pii/S0304394097009154

37. Xiong H, Yamada K, Han D, et al. Mutual regulation between the intercellular messengers nitric oxide and brain-derived neurotrophic factor in rodent neocortical neurons. Eur J Neurosci. 1999;11(5):1567-1576.http://onlinelibrary.wiley.com/doi/10.1046/j.1460-9568.1999.00567.x/abstract;jsessionid=8AC51B6C8235ABFB61C44182293DEF80.d03t03

38. Jin K, Graham SH, Nagayama T, et al. Altered expression of the neuropeptide-processing enzyme carboxypeptidase E in the rat brain after global ischemia. J Cereb Blood Flow Metab. 2001;21(12):1422-1429.http://www.nature.com/jcbfm/journal/v21/n12/full/9591174a.html#READ%20ME%20FIRST

39. Berman Y, Mzhavia N, Polonskaia A, et al. Defective prodynorphin processing in mice lacking prohormone convertase PC2. J Neurochem. 2000;75(4):1763-1770.http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2000.0751763.x/abstract;jsessionid=DE9BF0545B75C94CB7051DBCA2D43455.d04t01

40. Zhu X, Rouille Y, Lamango NS, et al. Internal cleavage of the inhibitory 7B2 carboxyl-terminal peptide by PC2: a potential mechanism for its inactivation. Proc Natl Acad Sci U S A. 1996;93(10):4919-4924.http://www.pnas.org/content/93/10/4919.long

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