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Abstract:

Heme Oxygenase-1 (HO-1), a stress- responsive enzyme which catalyzes heme degradation into iron, carbon monoxide, and biliverdin, exerts a neuroprotective role involving many different signaling pathways. In Parkinson disease patients, elevated HO-1 expression levels in astrocytes are involved in antioxidant defense. In the present work, employing an in vitro model of Mn2+-induced Parkinsonism in astroglial C6 cells, we investigated the role of HO-1 in both apoptosis and mitochondrial quality control (MQC). HO-1 exerted a protective effect against Mn2+ injury. In fact, HO-1 decreased both intracellular and mitochondrial reactive oxygen species as well as the appearance of apoptotic features. Considering that Mn2+ induces mitochondrial damage and a defective MQC has been implicated in neurodegenerative diseases, we hypothesized that HO-1 could mediate cytoprotection by regulating the MQC processes. Results obtained provide the first evidence that the beneficial effects of HO-1 in astroglial cells are mediated by the maintenance of both mitochondrial fusion/fission and biogenesis/mitophagy balances. Altogether, our data demonstrate a pro-survival function for HO-1 in Mn2+-induced apoptosis that involves the preservation of a proper MQC. These findings point to HO-1 as a new therapeutic target linked to mitochondrial pathophysiology in Manganism and probably Parkinson´s disease. © 2018

Registro:

Documento: Artículo
Título:Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control
Autor:Gorojod, R.M.; Alaimo, A.; Porte Alcon, S.; Martinez, J.H.; Cortina, M.E.; Vazquez, E.S.; Kotler, M.L.
Filiación:CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Disfunción Celular en Enfermedades Neurodegenerativas y Nanomedicina. Buenos Aires, Argentina
CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica (CM1), Laboratorio Interdisciplinario de Dinámica Celular y Nanoherramientas. Buenos Aires, Argentina
CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica (CM1), Laboratorio de Inflamación y Cáncer. Buenos Aires, Argentina
CONICET- Universidad de Buenos Aires, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica (CM1), Laboratorio Interdisciplinario de Dinámica Celular y Nanoherramientas. Buenos Aires, Argentina
Palabras clave:Astroglia; Heme Oxygenase-1; Manganese; Manganism; Mitochondrial quality control; Oxidative stress; heme oxygenase 1; manganese chloride; reactive oxygen metabolite; recombinant enzyme; recombinant heme oxygenase 1; unclassified drug; chloride; heme oxygenase 1; HMOX1 protein, human; manganese chloride; manganese derivative; reactive oxygen metabolite; animal cell; apoptosis; Article; astrocyte; cell damage; cell protection; controlled study; degenerative disease; in vitro study; macroglia; mitochondrial biogenesis; mitochondrial quality control; mitophagy; neuroprotection; nonhuman; oxidative stress; parkinsonism; priority journal; protein function; quality control; animal; astrocyte; chemically induced; dose response; drug effect; enzymology; intoxication; metabolism; mitochondrial dynamics; mitochondrion; oxidative stress; pathology; rat; signal transduction; time factor; tumor cell line; Animals; Apoptosis; Astrocytes; Cell Line, Tumor; Chlorides; Dose-Response Relationship, Drug; Heme Oxygenase-1; Manganese Compounds; Manganese Poisoning; Mitochondria; Mitochondrial Degradation; Mitochondrial Dynamics; Oxidative Stress; Parkinsonian Disorders; Rats; Reactive Oxygen Species; Signal Transduction; Time Factors
Año:2018
Volumen:295
Página de inicio:357
Página de fin:368
DOI: http://dx.doi.org/10.1016/j.toxlet.2018.07.045
Título revista:Toxicology Letters
Título revista abreviado:Toxicol. Lett.
ISSN:03784274
CODEN:TOLED
CAS:manganese chloride, 11132-78-8, 7773-01-5; chloride, 16887-00-6; Chlorides; Heme Oxygenase-1; HMOX1 protein, human; manganese chloride; Manganese Compounds; Reactive Oxygen Species
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03784274_v295_n_p357_Gorojod

Referencias:

  • Agarwal, A., Bolisetty, S., Adaptive responses to tissue injury: role of heme Oxygenase-1 (2013) Trans. Am. Clin. Climatol. Assoc., 124, pp. 111-122
  • Alaimo, A., Gorojod, R.M., Kotler, M.L., The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells (2011) Neurochem. Int., 59, pp. 297-308
  • Alaimo, A., Gorojod, R.M., Miglietta, E.A., Villarreal, A., Ramos, A.J., Kotler, M.L., Manganese induces mitochondrial dynamics impairment and apoptotic cell death: a study in human Gli36 cells (2013) Neurosci. Lett., 554, pp. 76-81
  • Alaimo, A., Gorojod, R.M., Beauquis, J., Muñoz, M.J., Saravia, F., Kotler, M.L., Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis (2014) PLoS ONE, 9
  • Andersen, J.K., Oxidative stress in neurodegeneration: cause or consequence? (2004) Nat. Med., 10, pp. S18-25
  • Aschner, M., Gannon, M., Kimelberg, H.K., Manganese uptake and efflux in cultured rat astrocytes (1992) J. Neurochem., 58, pp. 730-735
  • Cuadrado, A., Rojo, A.I., Heme oxygenase-1 as a therapeutic target in neurodegenerative diseases and brain infections (2008) Curr. Pharm. Des., 14, pp. 429-442
  • Dagda, R.K., Cherra, S.J., Kulich, S.M., Tandon, A., Park, D., Chu, C.T., Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission (2009) J. Biol. Chem., 284, pp. 13843-13855
  • Dupuis, L., Mitochondrial quality control in neurodegenerative diseases (2014) Biochimie, 100, pp. 177-183
  • Exil, V., Ping, L., Yu, Y., Chakraborty, S., Caito, S.W., Wells, K.S., Karki, P., Aschner, M., Activation of MAPK and FoxO by manganese (Mn) in rat neonatal primary astrocyte cultures (2014) PLoS ONE, 9
  • Fernández-Checa, J.C., Fernández, A., Morales, A., Marí, M., García-Ruiz, C., Colell, A., Oxidative stress and altered mitochondrial function in neurodegenerative diseases: lessons from mouse models (2010) CNS Neurol. Disord. Drug Targets, 9, pp. 439-454
  • Gonzalez, L.E., Juknat, A.A., Venosa, A.J., Verrengia, N., Kotler, M.L., Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family (2008) Neurochem. Int., 53, pp. 408-415
  • Gorojod, R.M., Alaimo, A., Porte Alcon, S., Pomilio, C., Saravia, F., Kotler, M.L., The autophagic- lysosomal pathway determines the fate of glial cells under manganese- induced oxidative stress conditions (2015) Free Radic. Biol. Med., 87, pp. 237-251
  • Gorojod, R.M., Alaimo, A., Porte Alcon, S., Saravia, F., Kotler, M.L., Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells (2017) Arch. Toxicol., 91, pp. 3065-3078
  • Gozzelino, R., Jeney, V., Soares, M.P., Mechanisms of cell protection by heme oxygenase-1 (2010) Annu. Rev. Pharmacol. Toxicol., 50, pp. 323-354
  • Gunter, T.E., Gavin, C.E., Aschner, M., Gunter, K.K., Speciation of manganese in cells and mitochondria: a search for the proximal cause of manganese neurotoxicity (2006) Neurotoxicology, 27, pp. 765-776
  • Hettiarachchi, N.T., Boyle, J.P., Dallas, M.L., Al-Owais, M.M., Scragg, J.L., Peers, C., Heme oxygenase-1 derived carbon monoxide suppresses Aβ1–42 toxicity in astrocytes (2017) Cell Death Dis., 8, p. e2884
  • Hull, T.D., Boddu, R., Guo, L., Tisher, C.C., Traylor, A.M., Patel, B., Joseph, R., George, J.F., Heme oxygenase-1 regulates mitochondrial quality control in the heart (2016) JCI Insight, 1, p. e85817
  • Jiang, J.K., Ma, X., Wu, Q.Y., Qian, W.B., Wang, N., Shi, S.S., Han, J.L., Wan, C.H., Upregulation of mitochondrial protease HtrA2/Omi contributes to manganese-induced neuronal apoptosis in rat brain striatum (2014) Neuroscience, 268, pp. 169-179
  • Jin, Y., Liu, X., Liu, H., Chen, S., Gao, C., Ge, K., Zhang, C., Zhang, J., Oxidative stress-induced apoptosis of osteoblastic MC3T3-E1 cells by hydroxyapatite nanoparticles through lysosomal and mitochondrial pathways (2017) RSC Adv., 7, pp. 13010-13018
  • Kappas, A., Drummond, G.S., Control of heme metabolism with synthetic metalloporphyrins (1986) J. Clin. Invest., 77, pp. 335-339
  • Kappas, A., Drummond, G.S., Simionatto, C.S., Anderson, K.E., Control of heme oxygenase and plasma levels of bilirubin by a synthetic heme analogue, tin-protoporphyrin (1984) Hepatology, 4, pp. 336-341
  • Kroemer, G., Mariño, G., Levine, B., Autophagy and the integrated stress response (2010) Mol. Cell, 40, pp. 280-293
  • Li, H., Wu, S., Shi, N., Lian, S., Lin, W., Nrf2/HO-1 pathway activation by manganese is associated with reactive oxygen species and ubiquitin-proteasome pathway, not MAPKs signaling (2011) J. Appl. Toxicol., 31, pp. 690-697
  • Li, H., Wu, S., Shi, N., Lin, W., You, J., Zhou, W., NF-E2-related factor 2 activation in PC12 cells: its protective role in manganese-induced damage (2011) Arch. Toxicol., 85, pp. 901-910
  • MacGarvey, N.C., Suliman, H.B., Bartz, R.R., Fu, P., Withers, C.M., Welty-Wolf, K.E., Piantadosi, C.A., Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis (2012) Am. J. Respir. Crit. Care Med., 185, pp. 851-861
  • Martin, D., Rojo, A.I., Salinas, M., Diaz, R., Gallardo, G., Alam, J., De Galarreta, C.M.R., Cuadrado, A., Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol (2004) J. Biol. Chem., 279, pp. 8919-8929
  • Milatovic, D., Yin, Z., Gupta, R.C., Sidoryk, M., Albrecht, J., Aschner, J.L., Aschner, M., Manganese induces oxidative impairment in cultured rat astrocytes (2007) Toxicol. Sci., 98, pp. 198-205
  • Morita, K., Lee, M.-S., Her, S., Possible relation of hemin-induced HO-1 expression to the upregulation of VEGF and BDNF mRNA levels in rat C6 glioma cells (2009) J. Mol. Neurosci., 38, pp. 31-40
  • Palikaras, K., Lionaki, E., Tavernarakis, N., Balancing mitochondrial biogenesis and mitophagy to maintain energy metabolism homeostasis (2015) Cell Death Differ., 22, pp. 1399-1401
  • Park, E., Chun, H.S., Protective effects of curcumin on manganese-induced BV-2 microglial cell death (2017) Biol. Pharm. Bull., 40, pp. 1275-1281
  • Piantadosi, C.A., Carraway, M.S., Babiker, A., Suliman, H.B., Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1 (2008) Circ. Res., 103, pp. 1232-1240
  • Piantadosi, C.A., Withers, C.M., Bartz, R.R., MacGarvey, N.C., Fu, P., Sweeney, T.E., Welty-Wolf, K.E., Suliman, H.B., Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression (2011) J. Biol. Chem., 286, pp. 16374-16385
  • Prabhakaran, K., Chapman, G.D., Gunasekar, P.G., BNIP3 up-regulation and mitochondrial dysfunction in manganese-induced neurotoxicity (2009) Neurotoxicology, 30, pp. 414-422
  • Robinson, K.M., Janes, M.S., Beckman, J.S., The selective detection of mitochondrial superoxide by live cell imaging (2008) Nat. Protoc., 3, pp. 941-947
  • Roth, J.A., Are there common biochemical and molecular mechanisms controlling manganism and parkisonism (2009) Neuromolecular Med., 11, pp. 281-296
  • Ryter, S.W., Choi, A.M.K., Heme oxygenase-1: molecular mechanisms of gene expression in oxygen-related stress (2002) Antioxid. Redox Signal., 4, pp. 625-632
  • Ryter, S.W., Xi, S., Hartsfield, C.L., Choi, A.M.K., Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells (2002) Antioxid. Redox Signal., 4, pp. 587-592
  • Ryter, S.W., Alam, J., Choi, A.M.K., Heme Oxygenase-1/Carbon monoxide: from basic science to therapeutic applications (2006) Physiol. Rev., 86, pp. 583-650
  • Sardana, M.K., Kappas, A., Dual control mechanism for heme oxygenase: tin(IV)-protoporphyrin potently inhibits enzyme activity while markedly increasing content of enzyme protein in liver (1987) Proc. Natl. Acad. Sci. U.S.A., 84, pp. 2464-2468
  • Schipper, H.M., Heme oxygenase-1 in Alzheimer disease: a tribute to Moussa Youdim (2011) J. Neural Transm., 118, pp. 381-387
  • Schmidt, J., Mertz, K., Morgan, J.I., Regulation of heme oxygenase-1 expression by dopamine in cultured C6 glioma and primary astrocytes (1999) Brain Res. Mol. Brain Res., 73, pp. 50-59
  • Sridharan, S., Jain, K., Basu, A., Regulation of autophagy by kinases (2011) Cancers, 3, pp. 2630-2654
  • Srisook, K., Jung, N.-H., Kim, B.-R., Cha, S.-H., Kim, H.-S., Cha, Y.-N., Heme oxygenase-1-mediated partial cytoprotective effect by NO on cadmium-induced cytotoxicity in C6 rat glioma cells (2005) Toxicol. In Vitro, 19, pp. 31-39
  • Suliman, H.B., Piantadosi, C.A., Mitochondrial quality control as a therapeutic target (2016) Pharmacol. Rev., 68, pp. 20-48
  • Taka, E., Mazzio, E., Soliman, K.F.A., Renee Reams, R., Microarray genomic profile of mitochondrial and oxidant response in manganese chloride treated PC12 cells (2012) Neurotoxicology, 33, pp. 162-168
  • Tenhunen, R., Marver, H.S., Schmid, R., The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase (1968) Proc. Natl. Acad. Sci. U.S.A., 61, pp. 748-755
  • Tenhunen, R., Marver, H.S., Schmid, R., The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin (1970) J. Lab. Clin. Med., 75, pp. 410-421
  • Wada, T., Penninger, J.M., Mitogen-activated protein kinases in apoptosis regulation (2004) Oncogene, 23, pp. 2838-2849
  • Wagener, F.A.D.T.G., Volk, H.-D., Willis, D., Abraham, N.G., Soares, M.P., Adema, G.J., Figdor, C.G., Different faces of the heme-Heme oxygenase system in inflammation (2003) Pharmacol. Rev., 55, pp. 551-571
  • Westermann, B., Mitochondrial fusion and fission in cell life and death (2010) Nat. Rev. Mol. Cell Biol., 11, pp. 872-884
  • Yu, J., Shi, J., Wang, D., Dong, S., Zhang, Y., Wang, M., Gong, L., Liu, D., Heme Oxygenase-1/Carbon monoxide-regulated mitochondrial dynamic equilibrium contributes to the attenuation of endotoxin-induced acute lung injury in rats and in lipopolysaccharide-activated macrophages (2016) Anesthesiology, 125, pp. 1190-1201
  • Yu, J., Wang, Y., Li, Z., Dong, S., Wang, D., Gong, L., Shi, J., Mu, R., Effect of heme Oxygenase-1 on Mitofusin-1 protein in LPS-induced ALI/ARDS in rats (2016) Sci. Rep., 6, p. 36530
  • Zhang, X., Bedard, E.L., Potter, R., Zhong, R., Alam, J., Choi, A.M.K., Lee, P.J., Mitogen-activated protein kinases regulate HO-1 gene transcription after ischemia-reperfusion lung injury (2002) Am. J. Physiol. Lung Cell Mol. Physiol., 283, pp. L815-829
  • Zheng, B., Liao, Z., Locascio, J.J., Lesniak, K.A., Roderick, S.S., Watt, M.L., Eklund, A.C., Global PD Gene Expression (GPEX) Consortium, PGC-1α a potential therapeutic target for early intervention in Parkinson's disease (2010) Sci. Transl. Med., 2

Citas:

---------- APA ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S. & Kotler, M.L. (2018) . Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control. Toxicology Letters, 295, 357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045
---------- CHICAGO ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S., et al. "Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control" . Toxicology Letters 295 (2018) : 357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045
---------- MLA ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S., et al. "Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control" . Toxicology Letters, vol. 295, 2018, pp. 357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045
---------- VANCOUVER ----------
Gorojod, R.M., Alaimo, A., Porte Alcon, S., Martinez, J.H., Cortina, M.E., Vazquez, E.S., et al. Heme Oxygenase-1 protects astroglia against manganese-induced oxidative injury by regulating mitochondrial quality control. Toxicol. Lett. 2018;295:357-368.
http://dx.doi.org/10.1016/j.toxlet.2018.07.045