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Pathophysiological Roles of ASK1-MAP Kinase Signaling Pathways

  • Nagai, Hiroaki (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, CREST, Japan Science and Technology Corporation, and Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, Center of Excellence (COE) program) ;
  • Noguchi, Takuya (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, CREST, Japan Science and Technology Corporation, and Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, Center of Excellence (COE) program) ;
  • Takeda, Kohsuke (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, CREST, Japan Science and Technology Corporation, and Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, Center of Excellence (COE) program) ;
  • Ichijo, Hidenori (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, CREST, Japan Science and Technology Corporation, and Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, Center of Excellence (COE) program)
  • Published : 2007.01.31

Abstract

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogenactivated protein kinase (MAPK) kinase kinase that activates JNK and p38 kinases. ASK1 is activated by various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx which are thought to be responsible for the pathogenesis or exacerbations of various human diseases. Recent studies revealed the involvement of ASK1 in ROS- or ER stressrelated diseases, suggesting that ASK1 may be a potential therapeutic target of various human diseases. In this review, we focus on the current findings for the relationship between pathogenesis and ASK1-MAPK pathways.

Keywords

References

  1. Aridor, M. and Balch, W. E. (1999) Integration of endoplasmic reticulum signaling in health and disease. Nat. Med. 5, 745-751. https://doi.org/10.1038/10466
  2. Behl, C., Davis, J. B., Lesley, R. and Schubert, D. (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77, 817-827. https://doi.org/10.1016/0092-8674(94)90131-7
  3. Bijangi-Vishehsaraei, K., Saadatzadeh, M. R., Werne, A., McKenzie, K. A., Kapur, R., Ichijo, H. and Haneline, L. S. (2005) Enhanced TNF-alpha-induced apoptosis in Fanconi anemia type C-deficient cells is dependent on apoptosis signalregulating kinase 1. Blood 106, 4124-4130. https://doi.org/10.1182/blood-2005-04-1434
  4. Bonifati, V., Rizzu, P., Squitieri, F., Krieger, E., Vanacore, N., van Swieten, J. C., Brice, A., van Duijn, C. M., Oostra, B., Meco, G. and Heutink, P. (2003) DJ-1 (PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol. Sci. 24, 159-160. https://doi.org/10.1007/s10072-003-0108-0
  5. Cleveland, D. W. and Rothstein, J. D. (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci. 2, 806-819. https://doi.org/10.1038/35097565
  6. Finkel, T. (2003) Oxidant signals and oxidative stress. Curr. Opin. Cell. Biol. 15, 247-254. https://doi.org/10.1016/S0955-0674(03)00002-4
  7. Geleziunas, R., Xu, W., Takeda, K., Ichijo, H. and Greene, W. C. (2001) HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell. Nature 410, 834-838. https://doi.org/10.1038/35071111
  8. Hayakawa, T., Matsuzawa, A., Noguchi, T., Takeda, K. and Ichijo, H. (2006) The ASK1-MAP kinase pathways in immune and stress responses. Microbes Infect. 8, 1098-1107. https://doi.org/10.1016/j.micinf.2005.03.023
  9. Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. A. and Butterfield, D. A. (1994) A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc. Natl. Acad. Sci. USA 91, 3270-3274. https://doi.org/10.1073/pnas.91.8.3270
  10. Holasek, S. S., Wengenack, T. M., Kandimalla, K. K., Montano, C., Gregor, D. M., Curran, G. L. and Poduslo, J. F. (2005). Activation of the stress-activated MAP kinase, p38, but not JNK in cortical motor neurons during early presymptomatic stages of amyotrophic lateral sclerosis in transgenic mice. Brain Res. 1045, 185-198. https://doi.org/10.1016/j.brainres.2005.03.037
  11. Izumi, Y., Kim, S., Yoshiyama, M., Izumiya, Y., Yoshida, K., Matsuzawa, A., Koyama, H., Nishizawa, Y., Ichijo, H., Yoshikawa, J. and Iwao, H. (2003). Activation of apoptosis signal-regulating kinase 1 in injured artery and its critical role in neointimal hyperplasia. Circulation 108, 2812-2818. https://doi.org/10.1161/01.CIR.0000069947.13421.2E
  12. Izumi, Y., Kim-Mitsuyama, S., Yoshiyama, M., Omura, T., Shiota, M., Matsuzawa, A., Yukimura, T., Murohara, T., Takeya, M., Ichijo, H., Yoshikawa, J. and Iwao, H. (2005) Important role of apoptosis signal-regulating kinase 1 in ischemia-induced angiogenesis. Arterioscler. Thromb. Vasc. Biol. 25, 1877-1883. https://doi.org/10.1161/01.ATV.0000174801.76234.bd
  13. Izumiya, Y., Kim, S., Izumi, Y., Yoshida, K., Yoshiyama, M., Matsuzawa, A., Ichijo, H., and Iwao, H. (2003) Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin IIinduced cardiac hypertrophy and remodeling. Circ. Res. 93, 874-883. https://doi.org/10.1161/01.RES.0000082767.38055.03
  14. Jibiki, I., Hashimoto, S., Maruoka, S., Gon, Y., Matsuzawa, A., Nishitoh, H., Ichijo, H. and Horie, T. (2003) Apoptosis signalregulating kinase 1-mediated signaling pathway regulates nitric oxide-induced activator protein-1 activation in human bronchial epithelial cells. Am. J. Respir. Crit. Care Med. 167, 856-861. https://doi.org/10.1164/rccm.2210005
  15. Junn, E., Taniguchi, H., Jeong, B. S., Zhao, X., Ichijo, H. and Mouradian, M. M. (2005). Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc. Natl. Acad. Sci. USA 102, 9691-9696. https://doi.org/10.1073/pnas.0409635102
  16. Kadowaki, H., Nishitoh, H., Urano, F., Sadamitsu, C., Matsuzawa, A., Takeda, K., Masutani, H., Yodoi, J., Urano, Y., Nagano, T. and Ichijo, H. (2005) Amyloid beta induces neuronal cell death through ROS-mediated ASK1 activation. Cell Death Differ. 12, 19-24. https://doi.org/10.1038/sj.cdd.4401495
  17. Kakizuka, A. (1998) Protein precipitation: a common etiology in neurodegenerative disorders? Trends Genet. 14, 396-402. https://doi.org/10.1016/S0168-9525(98)01559-5
  18. Kaufman, R. J. (2002) Orchestrating the unfolded protein response in health and disease. J. Clin. Invest. 110, 1389-1398. https://doi.org/10.1172/JCI0216886
  19. Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y. and Shimizu, N. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608. https://doi.org/10.1038/33416
  20. Kopito, R. R. and Ron, D. (2000) Conformational disease. Nat. Cell Biol. 2, 207-209. https://doi.org/10.1038/35041139
  21. Kumasawa, F., Hashimoto, S., Onose, A., Jibiki, I., Mizumura, K., Matsumoto, K., Maruoka, S., Gon, Y., Kobayashi, T., Takahashi, N., Ichijo, H. and Horie, T. (2005) Apoptosis signal-regulating kinase 1 in leukotriene D(4)-induced activator protein-1 activation in airway smooth muscle cells. Eur. J. Pharmacol. 517, 11-16. https://doi.org/10.1016/j.ejphar.2005.04.046
  22. Kyriakis, J. M. and Avruch, J. (2001) Mammalian mitogenactivated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 81, 807-869. https://doi.org/10.1152/physrev.2001.81.2.807
  23. Lang, A. E. and Lozano, A. M. (1998a) Parkinson's disease. First of two parts. N. Engl. J. Med. 339, 1044-1053. https://doi.org/10.1056/NEJM199810083391506
  24. Lang, A. E. and Lozano, A. M. (1998b) Parkinson's disease. Second of two parts. N. Engl. J. Med. 339, 1130-1143. https://doi.org/10.1056/NEJM199810153391607
  25. Machino, T., Hashimoto, S., Maruoka, S., Gon, Y., Hayashi, S., Mizumura, K., Nishitoh, H., Ichijo, H. and Horie, T. (2003). Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates hydrogen peroxide-induced apoptosis in human pulmonary vascular endothelial cells. Crit. Care Med. 31, 2776-2781. https://doi.org/10.1097/00003246-200301000-00001
  26. Maruoka, S., Hashimoto, S., Gon, Y., Nishitoh, H., Takeshita, I., Asai, Y., Mizumura, K., Shimizu, K., Ichijo, H. and Horie, T. (2003) ASK1 regulates influenza virus infection-induced apoptotic cell death. Biochem. Biophys. Res. Commun. 307, 870-876. https://doi.org/10.1016/S0006-291X(03)01116-1
  27. Matsuzawa, A., Saegusa, K., Noguchi, T., Sadamitsu, C., Nishitoh, H., Nagai, S., Koyasu, S., Matsumoto, K., Takeda, K. and Ichijo, H. (2005) ROS-dependent activation of the TRAF6- ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat. Immunol. 6, 587-592. https://doi.org/10.1038/ni1200
  28. Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A. and Yuan, J. (2000) Caspase-12 mediates endoplasmicreticulum- specific apoptosis and cytotoxicity by amyloid-beta. Nature 403, 98-103. https://doi.org/10.1038/47513
  29. Nishitoh, H., Matsuzawa, A., Tobiume, K., Saegusa, K., Takeda, K., Inoue, K., Hori, S., Kakizuka, A. and Ichijo, H. (2002) ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16, 1345-1355. https://doi.org/10.1101/gad.964002
  30. Nishitoh, H., Saitoh, M., Mochida, Y., Takeda, K., Nakano, H., Rothe, M., Miyazono, K. and Ichijo, H. (1998) ASK1 is essential for JNK/SAPK activation by TRAF2. Mol. Cell 2, 389-395. https://doi.org/10.1016/S1097-2765(00)80108-2
  31. Noguchi, T., Takeda, K., Matsuzawa, A., Saegusa, K., Nakano, H., Gohda, J., Inoue, J. and Ichijo, H. (2005) Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death. J. Biol. Chem. 280, 37033-37040. https://doi.org/10.1074/jbc.M506771200
  32. Saadatzadeh, M. R., Bijangi-Vishehsaraei, K., Hong, P., Bergmann, H. and Haneline, L. S. (2004) Oxidant hypersensitivity of Fanconi anemia type C-deficient cells is dependent on a redoxregulated apoptotic pathway. J. Biol. Chem. 279, 16805-16812. https://doi.org/10.1074/jbc.M313721200
  33. Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K. and Ichijo, H. (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 17, 2596-2606. https://doi.org/10.1093/emboj/17.1.1
  34. Sayama, K., Komatsuzawa, H., Yamasaki, K., Shirakata, Y., Hanakawa, Y., Ouhara, K., Tokumaru, S., Dai, X., Tohyama, M., Ten Dijke, P., Sugai, M., Ichijo, H. and Hashimoto, K. (2005) New mechanisms of skin innate immunity: ASK1- mediated keratinocyte differentiation regulates the expression of beta-defensins, LL37, and TLR2. Eur. J. Immunol. 35, 1886-1895. https://doi.org/10.1002/eji.200590000
  35. Sekine, Y., Takeda, K. and Ichijo, H. (2006) The ASK1-MAP kinase signaling in ER stress and neurodegenerative diseases. Curr. Mol. Med. 6, 87-97. https://doi.org/10.2174/156652406775574532
  36. Selkoe, D. J. (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. 81, 741-766. https://doi.org/10.1152/physrev.2001.81.2.741
  37. Shearman, M. S., Ragan, C. I. and Iversen, L. L. (1994) Inhibition of PC12 cell redox activity is a specific, early indicator of the mechanism of beta-amyloid-mediated cell death. Proc. Natl. Acad. Sci. USA 91, 1470-1474. https://doi.org/10.1073/pnas.91.4.1470
  38. Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K. and Suzuki, T. (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25, 302-305. https://doi.org/10.1038/77060
  39. Song, S., Kim, S. Y., Hong, Y. M., Jo, D. G., Lee, J. Y., Shim, S. M., Chung, C. W., Seo, S. J., Yoo, Y. J., Koh, J. Y., Lee, M. C., Yates, A. J., Ichijo, H. and Jung, Y. (2003) Essential role of E2-25K/Hip-2 in mediating amyloid-beta neurotoxicity. Mol. Cell 12, 553-563. https://doi.org/10.1016/j.molcel.2003.08.005
  40. Soto, C. (2003) Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. Neurosci. 4, 49-60. https://doi.org/10.1038/nrn1007
  41. Taira, T., Saito, Y., Niki, T., Iguchi-Ariga, S. M., Takahashi, K. and Ariga, H. (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep. 5, 213-218. https://doi.org/10.1038/sj.embor.7400074
  42. Takeda, K., Matsuzawa, A., Nishitoh, H., Tobiume, K., Kishida, S., Ninomiya-Tsuji, J., Matsumoto, K. and Ichijo, H. (2004) Involvement of ASK1 in $Ca^{2+}$-induced p38 MAP kinase activation. EMBO Rep. 5, 161-166. https://doi.org/10.1038/sj.embor.7400072
  43. Tobiume, K., Matsuzawa, A., Takahashi, T., Nishitoh, H., Morita, K., Takeda, K., Minowa, O., Miyazono, K., Noda, T. and Ichijo, H. (2001) ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep. 2, 222-228. https://doi.org/10.1093/embo-reports/kve046
  44. Tsujimoto, I., Hikoso, S., Yamaguchi, O., Kashiwase, K., Nakai, A., Takeda, T., Watanabe, T., Taniike, M., Matsumura, Y., Nishida, K., Hori, M., Kogo, M. and Otsu, K. (2005) The antioxidant edaravone attenuates pressure overload-induced left ventricular hypertrophy. Hypertension 45, 921-926. https://doi.org/10.1161/01.HYP.0000151326.48642.6c
  45. Watanabe, T., Otsu, K., Takeda, T., Yamaguchi, O., Hikoso, S., Kashiwase, K., Higuchi, Y., Taniike, M., Nakai, A., Matsumura, Y., Nishida, K., Ichijo, H. and Hori, M. (2005) Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death. Biochem. Biophys. Res. Commun. 333, 562-567. https://doi.org/10.1016/j.bbrc.2005.04.107
  46. Wengenack, T. M., Holasek, S. S., Montano, C. M., Gregor, D., Curran, G. L. and Poduslo, J. F. (2004) Activation of programmed cell death markers in ventral horn motor neurons during early presymptomatic stages of amyotrophic lateral sclerosis in a transgenic mouse model. Brain Res. 1027, 73-86. https://doi.org/10.1016/j.brainres.2004.08.054
  47. Widmann, C., Gibson, S., Jarpe, M. B. and Johnson, G. L. (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol. Rev. 79, 143-180. https://doi.org/10.1152/physrev.1999.79.1.143
  48. Yamaguchi, O., Higuchi, Y., Hirotani, S., Kashiwase, K., Nakayama, H., Hikoso, S., Takeda, T., Watanabe, T., Asahi, M., Taniike, M., et al. (2003) Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling. Proc. Natl. Acad. Sci. USA 100, 15883-15888. https://doi.org/10.1073/pnas.2136717100
  49. Yankner, B. A. (1996) Mechanisms of neuronal degeneration in Alzheimer's disease. Neuron 16, 921-932. https://doi.org/10.1016/S0896-6273(00)80015-X
  50. Zhang, Q., Zhang, G., Meng, F. and Tian, H. (2003) Biphasic activation of apoptosis signal-regulating kinase 1-stress-activated protein kinase 1-c-Jun N-terminal protein kinase pathway is selectively mediated by $Ca^{2+}$-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involving oxidative stress following brain ischemia in rat hippocampus. Neurosci. Lett. 337, 51-55. https://doi.org/10.1016/S0304-3940(02)01160-6

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  2. Japanese encephalitis virus down-regulates thioredoxin and induces ROS-mediated ASK1-ERK/p38 MAPK activation in human promonocyte cells vol.12, pp.8-9, 2010, https://doi.org/10.1016/j.micinf.2010.04.007
  3. Identification of novel ASK1 inhibitors using virtual screening vol.19, pp.1, 2011, https://doi.org/10.1016/j.bmc.2010.11.004
  4. Doing more than just the structure—structural genomics in kinase drug discovery vol.12, pp.1, 2008, https://doi.org/10.1016/j.cbpa.2008.01.042
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  12. Adipose stress-sensing kinases: linking obesity to malfunction vol.18, pp.8, 2007, https://doi.org/10.1016/j.tem.2007.08.006
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  46. A glycosylated antitumor ether lipid kills cells via paraptosis-like cell death vol.87, pp.2, 2009, https://doi.org/10.1139/O08-147
  47. Neuroprotective effects of liquiritigenin isolated from licorice roots on glutamate-induced apoptosis in hippocampal neuronal cells vol.39, 2013, https://doi.org/10.1016/j.neuro.2013.08.012
  48. Endoplasmic Reticulum Stress Plays a Pivotal Role in Cell Death Mediated by the Pan-Deacetylase Inhibitor Panobinostat in Human Hepatocellular Cancer Cells vol.6, pp.2, 2013, https://doi.org/10.1593/tlo.12271
  49. Knockdown of apoptosis signal-regulating kinase 1 affects ischaemia-induced astrocyte activation and glial scar formation vol.43, pp.7, 2016, https://doi.org/10.1111/ejn.13175
  50. ASK1 and MAP2K6 as modifiers of age at onset in Huntington’s disease vol.86, pp.4, 2008, https://doi.org/10.1007/s00109-007-0299-6
  51. Regulation of endothelial protein C receptor shedding by cytokines is mediated through differential activation of MAP kinase signaling pathways vol.315, pp.15, 2009, https://doi.org/10.1016/j.yexcr.2009.05.015
  52. Neuroprotective effects of neolignans isolated from Magnoliae Cortex against glutamate-induced apoptotic stimuli in HT22 cells vol.56, 2013, https://doi.org/10.1016/j.fct.2013.02.035
  53. 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 vol.34, pp.8, 2014, https://doi.org/10.1007/s10571-014-0089-y
  54. Targeting tissue oxidative damage by means of cell signaling modulators: The antioxidant concept revisited vol.128, pp.2, 2010, https://doi.org/10.1016/j.pharmthera.2010.08.003
  55. Colored Potato Extracts Induce Superoxide Dismutase-2 mRNA Via ERK1/2 Pathway in HepG2 Cells vol.65, pp.3, 2010, https://doi.org/10.1007/s11130-010-0171-7
  56. Coordinate Activation of Redox-Dependent ASK1/TGF-β Signaling by a Multiprotein Complex (MPK38, ASK1, SMADs, ZPR9, and TRX) Improves Glucose and Lipid Metabolism in Mice vol.24, pp.8, 2016, https://doi.org/10.1089/ars.2015.6325
  57. 4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Stress, Trypsin Activation, and Acinar Cell Apoptosis While Increasing Secretion in Rat Pancreatic Acini vol.42, pp.1, 2013, https://doi.org/10.1097/MPA.0b013e318259f6ca
  58. Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins Survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways vol.8, pp.1, 2008, https://doi.org/10.1186/1471-2407-8-129
  59. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis vol.87, pp.7, 2013, https://doi.org/10.1007/s00204-013-1034-4
  60. Adoptive passive transfer of rabbit β1-adrenoceptor peptide immune cardiomyopathy into the Rag2−/− mouse: Participation of the ER stress vol.44, pp.2, 2008, https://doi.org/10.1016/j.yjmcc.2007.11.007
  61. Procyanidin dimer B1 and trimer C1 impair inflammatory response signalling in human monocytes vol.45, pp.5, 2011, https://doi.org/10.3109/10715762.2011.564165
  62. Anticancer mechanisms and clinical application of alkylphospholipids vol.1831, pp.3, 2013, https://doi.org/10.1016/j.bbalip.2012.10.008
  63. ROS-dependent Activation of ASKI in Inflammatory Signaling vol.50, pp.2, 2008, https://doi.org/10.1016/S1349-0079(08)80024-2
  64. Chitosan oligosaccharides suppressant LPS binding to TLR4/MD-2 receptor complex vol.82, pp.2, 2010, https://doi.org/10.1016/j.carbpol.2010.04.079
  65. Binding of (-)-epigallocatechin-3-gallate to the Hsp70 ATPase domain may promote apoptosis in colorectal cancer vol.1, pp.1, 2008, https://doi.org/10.1093/biohorizons/hzn002
  66. Experimental Swine Lung Autotransplant Model to Study Lung Ischemia–Reperfusion Injury vol.47, pp.6, 2011, https://doi.org/10.1016/j.arbr.2011.02.002
  67. MAP kinase pathways in UV-induced apoptosis of retinal pigment epithelium ARPE19 cells vol.13, pp.3, 2008, https://doi.org/10.1007/s10495-008-0179-8
  68. Pyrogallol-induced As4.1 juxtaglomerular cell death is attenuated by MAPK inhibitors via preventing GSH depletion vol.84, pp.8, 2010, https://doi.org/10.1007/s00204-010-0526-8
  69. Casein Kinase 2 interacts with human mitogen- and stress-activated protein kinase MSK1 and phosphorylates it at Multiple sites vol.42, pp.12, 2009, https://doi.org/10.5483/BMBRep.2009.42.12.840
  70. HSP-70 mitigates LPS/SKI-induced cell damage by increasing sphingosine kinase 1 (SK1) vol.92, pp.1-4, 2010, https://doi.org/10.1016/j.prostaglandins.2009.12.006
  71. The Kelch Repeat Protein KLHDC10 Regulates Oxidative Stress-Induced ASK1 Activation by Suppressing PP5 vol.48, pp.5, 2012, https://doi.org/10.1016/j.molcel.2012.09.018
  72. Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress vol.32, pp.23, 2011, https://doi.org/10.1016/j.biomaterials.2011.04.024
  73. CRP promotes MMP-10 expression via c-Raf/MEK/ERK and JAK1/ERK pathways in cardiomyocytes vol.24, pp.3, 2012, https://doi.org/10.1016/j.cellsig.2011.11.019
  74. Reactive Oxygen Species and Hypertension: A Complex Association vol.10, pp.6, 2008, https://doi.org/10.1089/ars.2007.2012
  75. Review of Major Theories of Skin Aging vol.03, pp.04, 2014, https://doi.org/10.4236/aar.2014.34036
  76. β1 integrin/Fak/Src signaling in intestinal epithelial crypt cell survival: integration of complex regulatory mechanisms vol.13, pp.4, 2008, https://doi.org/10.1007/s10495-008-0192-y
  77. Berberine Ameliorates Pro-inflammatory Cytokine-Induced Endoplasmic Reticulum Stress in Human Intestinal Epithelial Cells In Vitro vol.35, pp.3, 2012, https://doi.org/10.1007/s10753-011-9385-6
  78. PTD-mediated delivery of anti-cell death proteins/peptides and therapeutic enzymes vol.60, pp.4-5, 2008, https://doi.org/10.1016/j.addr.2007.09.011
  79. Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro vol.130, pp.4, 2008, https://doi.org/10.1007/s00418-008-0421-z
  80. Signaling pathways from membrane lipid rafts to JNK1 activation in reactive nitrogen species-induced non-apoptotic cell death vol.15, pp.2, 2008, https://doi.org/10.1038/sj.cdd.4402273
  81. Buforin IIb induces endoplasmic reticulum stress-mediated apoptosis in HeLa cells vol.69, 2015, https://doi.org/10.1016/j.peptides.2015.04.024
  82. Oxyl radicals, redox-sensitive signalling cascades and antioxidants vol.19, pp.9, 2007, https://doi.org/10.1016/j.cellsig.2007.04.009
  83. Big Signals from Small Particles: Regulation of Cell Signaling Pathways by Nanoparticles vol.113, pp.5, 2013, https://doi.org/10.1021/cr3002627
  84. Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization vol.45, pp.8, 2012, https://doi.org/10.5483/BMBRep.2012.45.8.024
  85. Cryptotanshinone induces ER stress-mediated apoptosis in HepG2 and MCF7 cells vol.17, pp.3, 2012, https://doi.org/10.1007/s10495-011-0680-3
  86. Δ8-Tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: Involvement of cannabinoid receptor 2 and p38 MAPK vol.314, pp.2-3, 2013, https://doi.org/10.1016/j.tox.2013.10.007
  87. A Conclusive Review on Amyloid Beta Peptide Induced Cerebrovascular Degeneration and the Mechanism in Mitochondria vol.6, pp.3, 2013, https://doi.org/10.13160/ricns.2013.6.3.125
  88. A Synthesized Nostocionone Derivative Potentiates Programmed Cell Death in Human T-cell Leukemia Jurkat Cells Through Mitochondria via the Release of Endonuclease G vol.66, pp.8, 2014, https://doi.org/10.1080/01635581.2014.956255
  89. 2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone inhibits LPS-induced BV2 microglial activation through MAPK/NF-kB signaling pathways vol.2, pp.7, 2016, https://doi.org/10.1016/j.heliyon.2016.e00132
  90. Regulation of the Death-Associated Protein Kinase 1 Expression and Autophagy via ATF6 Requires Apoptosis Signal-Regulating Kinase 1 vol.34, pp.21, 2014, https://doi.org/10.1128/MCB.00397-14
  91. Cell Type-Specific Mechanisms in the Pathogenesis of Ischemic Stroke: The Role of Apoptosis Signal-Regulating Kinase 1 vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/2596043
  92. Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina vol.19, pp.11, 2018, https://doi.org/10.3390/ijms19113362
  93. The effect of reactive oxygen species on cardiomyocyte differentiation of pluripotent stem cells vol.52, pp.2, 2018, https://doi.org/10.1080/10715762.2017.1420184
  94. Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome vol.10, pp.5, 2018, https://doi.org/10.3390/toxins10050199