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Metabolic Brain Disease

, Volume 33, Issue 4, pp 1293–1306 | Cite as

Phosphodiesterase 4 and 7 inhibitors produce protective effects against high glucose-induced neurotoxicity in PC12 cells via modulation of the oxidative stress, apoptosis and inflammation pathways

  • Nazanin Namazi Sarvestani
  • Saeedeh Saberi Firouzi
  • Reza Falak
  • Mohammad Yahya Karimi
  • Mohammad Davoodzadeh Gholami
  • Akram Rangbar
  • Asieh Hosseini
Original Article
  • 133 Downloads

Abstract

Diabetic neuropathy (DN) is the most common diabetic complication. It is estimated diabetic population will increase to 592 million by the year 2035. This is while at least 50–60% of all diabetic patients will suffer from neuropathy in their lifetime. Oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation are crucial pathways in development and progression of DN. Since there is also no selective and effective therapeutic agent to prevent or treat high glucose (HG)-induced neuronal cell injury, it is crucial to explore tools by which one can reduce factors related to these pathways. Phosphodiesterase 4 and 7 (PDE 4 and 7) regulate oxidative damage, neurodegenaration, and inflammatory responses through modulation of cyclic adenosine monophosphate (cAMP) level, and thus can be as important drug targets for regulating DN. The aim of this study was to evaluate the protective effects of inhibitors of PDE 4 and 7, named rolipram and BRL5048, on HG-induced neurotoxicity in PC12 cells as an in vitro cellular model for DN and determine the possible mechanisms for theirs effects. We report that the PC12 cells pre-treatment with rolipram (2 μM) and/or BRL5048 (0.2 μM) for 60 min and then exposing the cells to HG (4.5 g/L for 72 h) or normal glucose (NG) (1 g/L for 72 h) condition show: (1) significant attenuation in ROS, MDA and TNF-a levels, Bax/Bcl-2 ratio, expression of caspase 3 and UCP2 proteins; (2) significant increase in viability, GSH/GSSG ratio, MMP and ATP levels. All these data together led us to propose PDE 4 and 7 inhibitors, and specifically, rolipram and BRL5048, as potential drugs candidate to be further studied for the prevention and treatment of DN.

Keywords

Diabetic neuropathy Phosphodiesterase 4 and 7 inhibitors High glucose PC12 cells, Neurotoxicity Oxidative damage Apoptosis Inflammation 

Notes

Acknowledgments

This study was supported by a grant from Iran University of Medical Sciences.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

References

  1. Alaamery MA, Wyman AR, Ivey FD, Allain C, Demirbas D, Wang L, Ceyhan O, Hoffman CS (2010) New classes of PDE7 inhibitors identified by a fission yeast-based HTS. J Biomol Screen 15(4):359–367.  https://doi.org/10.1177/1087057110362100 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Amicarelli F, Colafarina S, Cattani F, Cimini A, Di Ilio C, Ceru MP, Miranda M (2003) Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury. Free Radic Biol Med 35(8):856–871.  https://doi.org/10.1016/S0891-5849(03)00438-6 CrossRefPubMedGoogle Scholar
  3. Aminzadeh A (2017) Protective effect of tropisetron on high glucose induced apoptosis and oxidative stress in PC12 cells: roles of JNK, P38 MAPKs, and mitochondria pathway. Metab Brain Dis 32(3):819–826.  https://doi.org/10.1007/s11011-017-9976-5 CrossRefPubMedGoogle Scholar
  4. Aminzadeh A, Dehpour A, Safa M, Mirzamohammadi S, Sharifi A (2014) Investigating the protective effect of lithium against high glucose-induced neurotoxicity in PC12 cells: involvements of ROS, JNK and P38 MAPKs, and apoptotic mitochondria pathway. Cell Mol Neurobiol 34(8):1143–1150.  https://doi.org/10.1007/s10571-014-0089-y CrossRefPubMedGoogle Scholar
  5. Armstrong J, Steinauer K, Hornung B, Irish J, Lecane P, Birrell G, Peehl D, Knox S (2002) Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line. Cell Death Differ 9(3):252.  https://doi.org/10.1038/sj.cdd.4400959 CrossRefPubMedGoogle Scholar
  6. Bao F, Fleming JC, Golshani R, Pearse DD, Kasabov L, Brown A, Weaver LC (2011) A selective phosphodiesterase-4 inhibitor reduces leukocyte infiltration, oxidative processes, and tissue damage after spinal cord injury. J Neurotrauma 28(6):1035–1049.  https://doi.org/10.1089/neu.2010.1575 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58(3):488–520.  https://doi.org/10.1124/pr.58.3.5 CrossRefPubMedGoogle Scholar
  8. Block F, Schmidt W, Nolden-Koch M, Schwarz M (2001) Rolipram reduces excitotoxic neuronal damage. Neuroreport 12(7):1507–1511CrossRefPubMedGoogle Scholar
  9. Block F, Tondar A, Schmidt W, Schwarz M (1997) Delayed treatment with rolipram protects against neuronal damage following global ischemia in rats. Neuroreport 8(17):3829–3832CrossRefPubMedGoogle Scholar
  10. Boss O, Muzzin P, Giacobino J-P (1998) The uncoupling proteins, a review. Eur J Endocrinol 139(1):1–9.  https://doi.org/10.1530/eje.0.1390001 CrossRefPubMedGoogle Scholar
  11. Bournival J, Francoeur M-A, Renaud J, Martinoli M-G (2012) Quercetin and sesamin protect neuronal PC12 cells from high-glucose-induced oxidation, nitrosative stress, and apoptosis. Rejuvenation Res 15(3):322–333.  https://doi.org/10.1089/rej.2011.1242 CrossRefPubMedGoogle Scholar
  12. Brideau C, Van Staden C, Styhler A, Rodger IW, Chan CC (1999) The effects of phosphodiesterase type 4 inhibitors on tumour necrosis factor-α and leukotriene B4 in a novel human whole blood assay. Br J Pharmacol 126(4):979–988.  https://doi.org/10.1038/sj.bjp.0702387 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Christiansen SH, Selige J, Dunkern T, Rassov A, Leist M (2011) Combined anti-inflammatory effects of β 2-adrenergic agonists and PDE4 inhibitors on astrocytes by upregulation of intracellular cAMP. Neurochem Int 59(6):837–846.  https://doi.org/10.1016/j.neuint.2011.08.012 CrossRefPubMedGoogle Scholar
  14. Chung KF (2006) Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol 533(1):110–117.  https://doi.org/10.1016/j.ejphar.2005.12.059 CrossRefGoogle Scholar
  15. Conti M, Beavo J (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem 76:481–511.  https://doi.org/10.1146/annurev.biochem.76.060305.150444 CrossRefPubMedGoogle Scholar
  16. Costa LM, Pereira JE, Filipe VM, Magalhães LG, Couto PA, Gonzalo-Orden JM, Raimondo S, Geuna S, Maurício AC, Nikulina E (2013) Rolipram promotes functional recovery after contusive thoracic spinal cord injury in rats. Behav Brain Res 243:66–73.  https://doi.org/10.1016/j.bbr.2012.12.056 CrossRefPubMedGoogle Scholar
  17. Crilly A, Robertson SE, Reilly JH, Gracie JA, Lai W-Q, Leung BP, Life PF, McInnes IB (2011) Phosphodiesterase 4 (PDE4) regulation of proinflammatory cytokine and chemokine release from rheumatoid synovial membrane. Ann Rheum Dis Annrheumdis.  https://doi.org/10.1136/ard.2010.134825
  18. Cui Q, So KF (2004) Involvement of cAMP in neuronal survival and axonal regeneration. Anat Sci Int 79(4):209–212.  https://doi.org/10.1111/j.1447-073x.2004.00089.x CrossRefPubMedGoogle Scholar
  19. Cui Y, Xu X, Bi H, Zhu Q, Wu J, Xia X, Ren Q, Ho PC (2006) Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: the role of reactive oxygen species in diabetic retinopathy. Exp Eye Res 83(4):807–816.  https://doi.org/10.1016/j.exer.2006.03.024 CrossRefPubMedGoogle Scholar
  20. DeMarch Z, Giampà C, Patassini S, Bernardi G, Fusco FR (2008) Beneficial effects of rolipram in the R6/2 mouse model of Huntington's disease. Neurobiol Dis 30(3):375–387.  https://doi.org/10.1016/j.nbd.2008.02.010 CrossRefPubMedGoogle Scholar
  21. Esteves TC, Brand MD (2005) The reactions catalysed by the mitochondrial uncoupling proteins UCP2 and UCP3. Biochim Biophys Acta (BBA)-Bioenerg 1709(1):35–44.  https://doi.org/10.1016/j.bbabio.2005.06.002 CrossRefGoogle Scholar
  22. Fernyhough P, Huang TJ, Verkhratsky A (2003) Mechanism of mitochondrial dysfunction in diabetic sensory neuropathy. J Peripher Nerv Syst 8(4):227–235CrossRefPubMedGoogle Scholar
  23. Fortin M, D'Anjou H, Higgins M-È, Gougeon J, Aubé P, Moktefi K, Mouissi S, Séguin S, Séguin R, Renzi PM (2009) A multi-target antisense approach against PDE4 and PDE7 reduces smoke-induced lung inflammation in mice. Respir Res 10(1):39.  https://doi.org/10.1186/1465-9921-10-39 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Ghaznavi H, Najafi R, Mehrzadi S, Hosseini A, Tekyemaroof N, Shakeri-zadeh A, Rezayat M, Sharifi AM (2015) Neuro-protective effects of cerium and yttrium oxide nanoparticles on high glucose-induced oxidative stress and apoptosis in undifferentiated PC12 cells. Neurol Res 37(7):624–632CrossRefPubMedGoogle Scholar
  25. Ghosh R, Sawant O, Ganpathy P, Pitre S, Kadam V (2009) Phosphodiesterase inhibitors: their role and implications. Int J Pharm Tech Res 1(4):1148–1160Google Scholar
  26. Giembycz M, Smith S (2006) Phosphodiesterase 7A: a new therapeutic target for alleviating chronic inflammation? Curr Pharm Des 12(25):3207–3220.  https://doi.org/10.2174/138161206778194123 CrossRefPubMedGoogle Scholar
  27. Giembycz MA (2005) Life after PDE4: overcoming adverse events with dual-specificity phosphodiesterase inhibitors. Curr Opin Pharmacol 5(3):238–244.  https://doi.org/10.1016/j.coph.2005.04.001 CrossRefPubMedGoogle Scholar
  28. Gil C, Campillo NE, Perez DI, Martinez A (2008) PDE7 inhibitors as new drugs for neurological and inflammatory disorders. Expert Opin Ther Pat 18(10):1127–1139.  https://doi.org/10.1517/13543776.18.10.1127 CrossRefGoogle Scholar
  29. González-García C, Bravo B, Ballester A, Gómez-Pérez R, Eguiluz C, Redondo M, Martinez A, Gil C, Ballester S (2013) Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis. Br J Pharmacol 170(3):602–613.  https://doi.org/10.1111/bph.12308 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Greene DA, Stevens MJ, Obrosova I, Feldman EL (1999) Glucose-induced oxidative stress and programmed cell death in diabetic neuropathy. Eur J Pharmacol 375(1):217–223CrossRefPubMedGoogle Scholar
  31. Greene LA, Connolly JL, Viscarello RR et al (1979) Rapid, sequential changes in surface morphology of PC12 pheochromocytoma cells in response to nerve growth factor. J Cell Biol 82:820–827.  https://doi.org/10.1083/jcb.82.3.820 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Guo C, Quobatari A, Shangguan Y, Hong S, Wiley J (2004) Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat. Neurogastroenterol Motil 16(3):335–345.  https://doi.org/10.1111/j.1365-2982.2004.00524.x CrossRefPubMedGoogle Scholar
  33. Guo CH, Bai L, Wu HH, Yang J, Cai GH, Wang X, Wu SX, Ma W (2016) The analgesic effect of rolipram is associated with the inhibition of the activation of the spinal astrocytic JNK/CCL2 pathway in bone cancer pain. Int J Mol Med 38(5):1433–1442.  https://doi.org/10.3892/ijmm.2016.2763 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Hannila SS, Filbin MT (2008) The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol 209(2):321–332.  https://doi.org/10.1016/j.expneurol.2007.06.020 CrossRefPubMedGoogle Scholar
  35. Hosseini A, Abdollahi M (2013) Diabetic neuropathy and oxidative stress: therapeutic perspectives. Oxidative Med Cell Longev 2013.  https://doi.org/10.1155/2013/168039
  36. Hosseini A, Abdollahi M, Hassanzadeh G, Rezayat M, Hassani S, Pourkhalili N, Tabrizian K, Khorshidahmad T, Beyer C, Sharifzadeh M (2011) Protective Effect of Magnesium-25 Carrying Porphyrin-Fullerene Nanoparticles on Degeneration of Dorsal Root Ganglion Neurons and Motor Function in Experimental Diabetic Neuropathy. Basic Clin Pharmacol Toxicol 109(5):381–386CrossRefPubMedGoogle Scholar
  37. Hosseini A, Sharifzadeh M, Rezayat SM, Hassanzadeh G, Hassani S, Baeeri M, Shetab-Bushehri V, Kuznetsov DA, Abdollahi M (2010) Benefit of magnesium-25 carrying porphyrin-fullerene nanoparticles in experimental diabetic neuropathy. Int J Nanomedicine 5:517.  https://doi.org/10.2147/IJN.S11643 PubMedPubMedCentralCrossRefGoogle Scholar
  38. Houslay MD, Schafer P, Zhang KY (2005) Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 10(22):1503–1519.  https://doi.org/10.1016/S1359-6446(05)03622-6 CrossRefPubMedGoogle Scholar
  39. Huizinga MM, Peltier A (2007) Painful diabetic neuropathy: a management-centered review. Clin Diabetes 25(1):6–15CrossRefGoogle Scholar
  40. Iona S, Cuomo M, Bushnik T, Naro F, Sette C, Hess M, Shelton ER, Conti M (1998) Characterization of the rolipram-sensitive, cyclic AMP-specific phosphodiesterases: identification and differential expression of immunologically distinct forms in the rat brain. Mol Pharmacol 53(1):23–32CrossRefPubMedGoogle Scholar
  41. Johnson LV, Walsh ML, Bockus BJ, Chen LB (1981) Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy. J Cell Biol 88(3):526–535CrossRefPubMedGoogle Scholar
  42. Kajana S, Goshgarian HG (2009) Systemic administration of rolipram increases medullary and spinal cAMP and activates a latent respiratory motor pathway after high cervical spinal cord injury. J Spinal Cord Med 32(2):175–182CrossRefPubMedPubMedCentralGoogle Scholar
  43. Kim HK, Kwon JY, Yoo C, Abdi S (2015) The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on Chemotherapy-Induced Neuropathic Pain in Rats. Anesth Analg 121(3):822–828.  https://doi.org/10.1213/ANE.0000000000000853 CrossRefPubMedGoogle Scholar
  44. Kim-Han JS, Reichert SA, Quick KL, Dugan LL (2001) BMCP1: a mitochondrial uncoupling protein in neurons which regulates mitochondrial function and oxidant production. J Neurochem 79(3):658–668.  https://doi.org/10.1046/j.1471-4159.2001.00604.x CrossRefPubMedGoogle Scholar
  45. Kimmich GA, Randles J, Brand JS (1975) Assay of picomole amounts of ATP, ADP, and AMP using the luciferase enzyme system. Anal Biochem 69(1):187–206CrossRefPubMedGoogle Scholar
  46. Kishi M, Mitsui M, Nagamatsu M, Nickander K, Schmelzer J, Tanabe J, Yao J, Low P (2001) Dorsal root ganglion pathology in chronic experimental diabetic neuropathy. J Peripher Nerv Syst 6:152A–153AGoogle Scholar
  47. Knott AB, Perkins G, Schwarzenbacher R, Bossy-Wetzel E (2008) Mitochondrial fragmentation in neurodegeneration. Nat Rev Neurosci 9(7):505–518.  https://doi.org/10.1038/nrn2417 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Korhonen R, Hömmö T, Keränen T, Laavola M, Hämäläinen M, Vuolteenaho K, Lehtimäki L, Kankaanranta H, Moilanen E (2013) Attenuation of TNF production and experimentally induced inflammation by PDE4 inhibitor rolipram is mediated by MAPK phosphatase-1. Br J Pharmacol 169(7):1525–1536.  https://doi.org/10.1111/bph.12189 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Kraft P, Schwarz T, Göb E, Heydenreich N, Brede M, Meuth SG, Kleinschnitz C (2013) The phosphodiesterase-4 inhibitor rolipram protects from ischemic stroke in mice by reducing blood–brain-barrier damage, inflammation and thrombosis. Exp Neurol 247:80–90.  https://doi.org/10.1016/j.expneurol.2013.03.026 CrossRefPubMedGoogle Scholar
  50. Kroemer G (1997) The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 3(6):614–620CrossRefPubMedGoogle Scholar
  51. Lelkes E, Unsworth BR, Lelkes PI (2001) Reactive oxygen species, apoptosis and alte1red NGF-induced signaling in PC12 pheochromocytoma cells cultured in elevated glucose: AnIn Vitro cellular model for diabetic neuropathy. Neurotox Res 3(2):189–203CrossRefPubMedGoogle Scholar
  52. Lin C-H, Lin P-J, Chen Y-H, Lin P-L, Chen I-M, Lu K-L, Chang Y-C, Tsai M-C (2005) Effects of rolipram on induction of action potential bursts in central snail neurons. Exp Neurol 194(2):384–392.  https://doi.org/10.1016/j.expneurol.2005.02.016 CrossRefPubMedGoogle Scholar
  53. Liu MH, Yuan C, He J, Tan TP, Wu SJ, Fu HY, Liu J, Yu S, Chen YD, Le QF, Tian W, Hu HJ, Zhang Y, Lin XL (2015) Resveratrol protects PC12 cells from high glucose-induced neurotoxicity via PI3K/Akt/FoxO3a pathway. Cell Mol Neurobiol 35(4):513–522.  https://doi.org/10.1007/s10571-014-0147-5 CrossRefPubMedGoogle Scholar
  54. Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35(4):605–623CrossRefPubMedGoogle Scholar
  55. Menniti FS, Faraci WS, Schmidt CJ (2006) Phosphodiesterases in the CNS: targets for drug development. Nat Rev Drug Discov 5(8):660–670.  https://doi.org/10.1038/nrd2058 CrossRefPubMedGoogle Scholar
  56. Ming G-l, Song H-J, Berninger B, Holt CE, Tessier-Lavigne M, Poo M-M (1997) cAMP-dependent growth cone guidance by netrin-1. Neuron 19(6):1225–1235.  https://doi.org/10.1016/S0896-6273(00)80414-6 CrossRefPubMedGoogle Scholar
  57. Mirza S, Hossain M, Mathews C, Martinez P, Pino P, Gay JL, Rentfro A, McCormick JB, Fisher-Hoch SP (2012) Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine 57(1):136–142.  https://doi.org/10.1016/j.cyto.2011.09.029 CrossRefPubMedGoogle Scholar
  58. Mokry J, Joskova M, Mokra D, Christensen I, Nosalova G (2013) Effects of selective inhibition of PDE4 and PDE7 on airway reactivity and cough in healthy and ovalbumin-sensitized guinea pigs. In: Respiratory Regulation-The Molecular Approach, vol. Springer, pp 57–64.  https://doi.org/10.1007/978-94-007-4549-0_8
  59. Morales-Garcia JA, Alonso-Gil S, Gil C, Martinez A, Santos A, Perez-Castillo A (2015) Phosphodiesterase 7 inhibition induces dopaminergic neurogenesis in hemiparkinsonian rats. Stem Cells Transl Med 4(6):564–575.  https://doi.org/10.5966/sctm.2014-0277 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Morales-Garcia JA, Redondo M, Alonso-Gil S, Gil C, Perez C, Martinez A, Santos A, Perez-Castillo A (2011) Phosphodiesterase 7 inhibition preserves dopaminergic neurons in cellular and rodent models of Parkinson disease. PLoS One 6(2):e17240.  https://doi.org/10.1371/journal.pone.0017240 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Najafi R, Sharifi AM, Hosseini A (2015) Protective effects of alpha lipoic acid on high glucose-induced neurotoxicity in PC12 cells. Metab Brain Dis 30(3):731–738.  https://doi.org/10.1007/s11011-014-9625-1 CrossRefPubMedGoogle Scholar
  62. Nakata A, Ogawa K, Sasaki T, Koyama N, Wada K, Kotera J, Kikkawa H, Omori K, Kaminuma O (2002) Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. Clin Exp Immunol 128(3):460–466.  https://doi.org/10.1046/j.1365-2249.2002.01856.x CrossRefPubMedPubMedCentralGoogle Scholar
  63. Negi G, Kumar A, Sharma SS (2011) Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF-κB and Nrf2 cascades. J Pineal Res 50(2):124–131.  https://doi.org/10.1111/j.1600-079X.2010.00821.x PubMedCrossRefGoogle Scholar
  64. Nikulina E, Tidwell JL, Dai HN, Bregman BS, Filbin MT (2004) The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci U S A 101(23):8786–8790.  https://doi.org/10.1073/pnas.0402595101 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358CrossRefPubMedGoogle Scholar
  66. Parkkonen J, Hasala H, Moilanen E, Giembycz MA, Kankaanranta H (2008) Phosphodiesterase 4 inhibitors delay human eosinophil and neutrophil apoptosis in the absence and presence of salbutamol. Pulm Pharmacol Ther 21(3):499–506.  https://doi.org/10.1016/j.pupt.2007.11.003 CrossRefPubMedGoogle Scholar
  67. Paterniti I, Mazzon E, Gil C, Impellizzeri D, Palomo V, Redondo M, Perez DI, Esposito E, Martinez A, Cuzzocrea S (2011) PDE 7 inhibitors: new potential drugs for the therapy of spinal cord injury. PLoS One 6(1):e15937.  https://doi.org/10.1371/journal.pone.0015937 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Perez-Aso M, Montesinos MC, Mediero A, Wilder T, Schafer PH, Cronstein B (2015) Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. Arthritis Res Ther 17(1):249.  https://doi.org/10.1186/s13075-015-0771-6 CrossRefPubMedPubMedCentralGoogle Scholar
  69. Perez-Gonzalez R, Pascual C, Antequera D, Bolos M, Redondo M, Perez DI, Pérez-Grijalba V, Krzyzanowska A, Sarasa M, Gil C (2013) Phosphodiesterase 7 inhibitor reduced cognitive impairment and pathological hallmarks in a mouse model of Alzheimer's disease. Neurobiol Aging 34(9):2133–2145.  https://doi.org/10.1371/journal.pone.0017240 CrossRefPubMedGoogle Scholar
  70. Pickup JC, Chusney GD, Thomas SM, Burt D (2000) Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes. Life Sci 67(3):291–300.  https://doi.org/10.1016/S0024-3205(00)00622-6 CrossRefPubMedGoogle Scholar
  71. Radi E, Formichi P, Battisti C, Federico A (2014) Apoptosis and oxidative stress in neurodegenerative diseases. J Alzheimers Dis 42(s3):S125–S152.  https://doi.org/10.3233/JAD-132738 CrossRefPubMedGoogle Scholar
  72. Redondo M, Zarruk JG, Ceballos P, Pérez DI, Pérez C, Perez-Castillo A, Moro MA, Brea J, Val C, Cadavid MI (2012) Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model. Eur J Med Chem 47:175–185.  https://doi.org/10.1016/j.ejmech.2011.10.040 CrossRefPubMedGoogle Scholar
  73. Rezvanfar MA, Rezvanfar MA, Ranjbar A, Baeeri M, Mohammadirad A, Abdollahi M (2010) Biochemical evidence on positive effects of rolipram a phosphodiesterase-4 inhibitor in malathion-induced toxic stress in rat blood and brain mitochondria. Pestic Biochem Physiol 98(1):135–143.  https://doi.org/10.1016/j.pestbp.2010.06.001 CrossRefGoogle Scholar
  74. Rodger J, Goto H, Cui Q, Chen P, Harvey A (2005) cAMP regulates axon outgrowth and guidance during optic nerve regeneration in goldfish. Mol Cell Neurosci 30(3):452–464.  https://doi.org/10.1016/j.mcn.2005.08.009 CrossRefPubMedGoogle Scholar
  75. Rolo AP, Palmeira CM (2006) Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 212(2):167–178.  https://doi.org/10.1016/j.taap.2006.01.003 CrossRefPubMedGoogle Scholar
  76. Russell JW, Golovoy D, Vincent AM, Mahendru P, Olzmann JA, Mentzer A, Feldman EL (2002) High glucose-induced oxidative stress and mitochondrial dysfunction in neurons. FASEB J 16(13):1738–1748.  https://doi.org/10.1096/fj.01-1027com CrossRefPubMedGoogle Scholar
  77. Russell JW, Sullivan KA, Windebank AJ, Herrmann DN, Feldman EL (1999) Neurons undergo apoptosis in animal and cell culture models of diabetes. Neurobiol Dis 6(5):347–363.  https://doi.org/10.1006/nbdi.1999.0254 CrossRefPubMedGoogle Scholar
  78. Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A (2014) Neuroinflammation and oxidative stress in diabetic neuropathy: futuristic strategies based on these targets. Int J Endocrinol 2014:674987.  https://doi.org/10.1155/2014/674987 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Schaal SM, Garg MS, Ghosh M, Lovera L, Lopez M, Patel M, Louro J, Patel S, Tuesta L, Chan W-M (2012) The therapeutic profile of rolipram, PDE target and mechanism of action as a neuroprotectant following spinal cord injury. PLoS One 7(9):e43634.  https://doi.org/10.1371/journal.pone.0043634 CrossRefPubMedPubMedCentralGoogle Scholar
  80. Scherbel U, Raghupathi R, Nakamura M, Saatman KE, Trojanowski JQ, Neugebauer E, Marino MW, McIntosh TK (1999) Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci 96(15):8721–8726.  https://doi.org/10.1073/pnas.96.15.8721 CrossRefPubMedGoogle Scholar
  81. Serra-Pérez A, Verdaguer E, Planas AM, Santalucía T (2008) Glucose promotes caspase-dependent delayed cell death after a transient episode of oxygen and glucose deprivation in SH-SY5Y cells. J Neurochem 106(3):1237–1247.  https://doi.org/10.1111/j.1471-4159.2008 CrossRefPubMedGoogle Scholar
  82. Sharifi AM, Eslami H, Larijani B, Davoodi J (2009) Involvement of caspase-8,-9, and-3 in high glucose-induced apoptosis in PC12 cells. Neurosci Lett 459(2):47–51.  https://doi.org/10.1254/jphs.FP0070258 CrossRefPubMedGoogle Scholar
  83. Sharma V, Bala A, Deshmukh R, Bedi K, Sharma P (2012) Neuroprotective effect of RO-20-1724-a phosphodiesterase4 inhibitor against intracerebroventricular streptozotocin induced cognitive deficit and oxidative stress in rats. Pharmacol Biochem Behav 101(2):239–245.  https://doi.org/10.1016/j.pbb.2012.01.004 CrossRefPubMedGoogle Scholar
  84. Siddique YH, Ara G, Afzal M (2012) Estimation of lipid peroxidation induced by hydrogen peroxide in cultured human lymphocytes. Dose-Response 10(1).  https://doi.org/10.2203/dose-response
  85. Smith SJ, Cieslinski LB, Newton R, Donnelly LE, Fenwick PS, Nicholson AG, Barnes PJ, Barnette MS, Giembycz MA (2004) Discovery of BRL 50481 [3-(N, N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes. Mol Pharmacol 66(6):1679–1689.  https://doi.org/10.1124/mol.104.002246 CrossRefPubMedGoogle Scholar
  86. Sommer N, Martin R, McFarland H, Quigley L, Cannella B, Raine C, Scott D, Löschmann P-A, Racke M (1997) Therapeutic potential of phosphodiesterase type 4 inhibition in chronic autoimmune demyelinating disease. J Neuroimmunol 79(1):54–61.  https://doi.org/10.1016/S0165-5728(97)00111-2 CrossRefPubMedGoogle Scholar
  87. Souza BM, Assmann TS, Kliemann LM, Gross JL, Canani LH, Crispim D (2011) The role of uncoupling protein 2 (UCP2) on the development of type 2 diabetes mellitus and its chronic complications. Arq Bras Endocrinol Metabol 55(4):239–248.  https://doi.org/10.1590/S0004-27302011000400001 CrossRefPubMedGoogle Scholar
  88. Spina D (2003) Phosphodiesterase-4 inhibitors in the treatment of inflammatory lung disease. Drugs 63(23):2575–2259.  https://doi.org/10.2165/00003495-200363230-00002 CrossRefPubMedGoogle Scholar
  89. Srinivasan S, Stevens M, Wiley JW (2000) Diabetic peripheral neuropathy: evidence for apoptosis and associated mitochondrial dysfunction. Diabetes 49(11):1932–1938.  https://doi.org/10.2337/diabetes.49.11.1932 CrossRefPubMedGoogle Scholar
  90. Teixeira MM, Gristwood RW, Cooper N, Hellewell PG (1997) Phosphodiesterase (PDE) 4 inhibitors: anti-inflammatory drugs of the future? Trends Pharmacol Sci 18(5):164–170CrossRefPubMedGoogle Scholar
  91. Thakur T, Sharma S, Kumar K, Deshmukh R, Sharma PL (2013) Neuroprotective role of PDE4 and PDE5 inhibitors in 3-nitropropionic acid induced behavioral and biochemical toxicities in rats. Eur J Pharmacol 714(1):515–521.  https://doi.org/10.1016/j.ejphar.2013.06.035 CrossRefPubMedGoogle Scholar
  92. Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281(5381):1312–1316CrossRefPubMedGoogle Scholar
  93. Troadec J-D, Marien M, Mourlevat S, Debeir T, Ruberg M, Colpaert F, Michel PP (2002) Activation of the mitogen-activated protein kinase (ERK1/2) signaling pathway by cyclic AMP potentiates the neuroprotective effect of the neurotransmitter noradrenaline on dopaminergic neurons. Mol Pharmacol 62(5):1043–1052CrossRefPubMedGoogle Scholar
  94. Udina E, Ladak A, Furey M, Brushart T, Tyreman N, Gordon T (2010) Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration. Exp Neurol 223(1):143–152.  https://doi.org/10.1016/j.expneurol.2009.08.026 CrossRefPubMedGoogle Scholar
  95. Vijayakrishnan L, Rudra S, Eapen MS, Dastidar S, Ray A (2007) Small-molecule inhibitors of PDE-IV and-VII in the treatment of respiratory diseases and chronic inflammation. Expert Opin Investig Drugs 16(10):1585–1599.  https://doi.org/10.1517/13543784.16.10.1585 CrossRefPubMedGoogle Scholar
  96. Vincent AM, Olzmann JA, Brownlee M, Sivitz W, Russell JW (2004a) Uncoupling proteins prevent glucose-induced neuronal oxidative stress and programmed cell death. Diabetes 53(3):726–734.  https://doi.org/10.2337/diabetes.53.3.726 CrossRefPubMedGoogle Scholar
  97. Vincent AM, Russell JW, Low P, Feldman EL (2004b) Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev 25(4):612–628.  https://doi.org/10.1210/er.2003-0019 CrossRefPubMedGoogle Scholar
  98. Volakakis N, Kadkhodaei B, Joodmardi E, Wallis K, Panman L, Silvaggi J, Spiegelman BM, Perlmann T (2010) NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection. Proc Natl Acad Sci 107(27):12317–12322.  https://doi.org/10.1073/pnas.1007088107 CrossRefPubMedGoogle Scholar
  99. Wang C, Yang X-M, Zhuo Y-Y, Zhou H, Lin H-B, Cheng Y-F, Xu J-P, Zhang H-T (2012) The phosphodiesterase-4 inhibitor rolipram reverses Aβ-induced cognitive impairment and neuroinflammatory and apoptotic responses in rats. Int J Neuropsychopharmacol 15(6):749–766.  https://doi.org/10.1017/S1461145711000836 CrossRefPubMedGoogle Scholar
  100. Yan L-J (2014) Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J Diabetes Res 2014.  https://doi.org/10.1155/2014/137919
  101. Yang L, Calingasan NY, Lorenzo BJ, Beal MF (2008) Attenuation of MPTP neurotoxicity by rolipram, a specific inhibitor of phosphodiesterase IV. Exp Neurol 211(1):311–314.  https://doi.org/10.1016/j.expneurol.2007.02.010 CrossRefPubMedGoogle Scholar
  102. Zhuo Y, Guo H, Cheng Y, Wang C, Wang C, Wu J, Zou Z, Gan D, Li Y, Xu J (2016) Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25–35 in rats. Metab Brain Dis 31(4):779–791.  https://doi.org/10.1007/s11011-016-9814-1 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Animal Biology, School of Biology, Department of ScienceUniversity of TehranTehranIran
  2. 2.Department of Pharmacology, Faculty of MedicineTehran University of Medical SciencesTehranIran
  3. 3.Department of Immunology, School of MedicineIran University of Medical SciencesTehranIran
  4. 4.Razi Drug Research CenterIran University of Medical SciencesTehranIran
  5. 5.Department of Toxicology and Pharmacology, School of PharmacyHamadan University of Medical SciencesHamadanIran

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