Cross organelle stress response disruption promotes gentamicin-induced proteotoxicity.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
03 04 2020
03 04 2020
Historique:
received:
09
06
2019
accepted:
09
01
2020
revised:
19
12
2019
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
10
4
2021
Statut:
epublish
Résumé
Gentamicin is a nephrotoxic antibiotic that causes acute kidney injury (AKI) primarily by targeting the proximal tubule epithelial cell. The development of an effective therapy for gentamicin-induced renal cell injury is limited by incomplete mechanistic insight. To address this challenge, we propose that RNAi signal pathway screening could identify a unifying mechanism of gentamicin-induced cell injury and suggest a therapeutic strategy to ameliorate it. Computational analysis of RNAi signal screens in gentamicin-exposed human proximal tubule cells suggested the cross-organelle stress response (CORE), the unfolded protein response (UPR), and cell chaperones as key targets of gentamicin-induced injury. To test this hypothesis, we assessed the effect of gentamicin on the CORE, UPR, and cell chaperone function, and tested the therapeutic efficacy of enhancing cell chaperone content. Early gentamicin exposure disrupted the CORE, evidenced by a rise in the ATP:ADP ratio, mitochondrial-specific H
Identifiants
pubmed: 32245975
doi: 10.1038/s41419-020-2382-7
pii: 10.1038/s41419-020-2382-7
pmc: PMC7125232
doi:
Substances chimiques
Anti-Bacterial Agents
0
Gentamicins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
217Subventions
Organisme : NIDDK NIH HHS
ID : F30 DK117612
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215059
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001430
Pays : United States
Références
Fowler, V. G. Jr. et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N. Engl. J. Med. 355, 653–665 (2006).
pubmed: 16914701
doi: 10.1056/NEJMoa053783
Nagai, J. & Takano, M. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways. Biochem Pharm. 90, 331–337 (2014).
pubmed: 24881578
doi: 10.1016/j.bcp.2014.05.018
Cardile, V., Graziano, A. C., Avola, R., Piovano, M. & Russo, A. Potential anticancer activity of lichen secondary metabolite physodic acid. Chem. Biol. Interact. 263, 36–45 (2017).
pubmed: 28012710
doi: 10.1016/j.cbi.2016.12.007
Tangy, F., Moukkadem, M., Vindimian, E., Capmau, M. L. & Le Goffic, F. Mechanism of action of gentamicin components. Characteristics of their binding to Escherichia coli ribosomes. Eur. J. Biochem. 147, 381–386 (1985).
pubmed: 3882427
doi: 10.1111/j.1432-1033.1985.tb08761.x
Jaikumkao, K. et al. Amelioration of renal inflammation, endoplasmic reticulum stress and apoptosis underlies the protective effect of low dosage of atorvastatin in gentamicin-induced nephrotoxicity. PLoS ONE 11, e0164528 (2016).
pubmed: 27727327
pmcid: 5058561
doi: 10.1371/journal.pone.0164528
Lopez-Novoa, J. M., Quiros, Y., Vicente, L., Morales, A. I. & Lopez-Hernandez, F. J. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 79, 33–45 (2011).
pubmed: 20861826
doi: 10.1038/ki.2010.337
Peyrou, M., Hanna, P. E. & Cribb, A. E. Cisplatin, gentamicin, and p-aminophenol induce markers of endoplasmic reticulum stress in the rat kidneys. Toxicol. Sci. 99, 346–353 (2007).
pubmed: 17567590
doi: 10.1093/toxsci/kfm152
Prokhorova, I. et al. Aminoglycoside interactions and impacts on the eukaryotic ribosome. Proc. Natl Acad. Sci. USA 114, E10899–E10908 (2017).
pubmed: 29208708
doi: 10.1073/pnas.1715501114
Brehme, M. & Voisine, C. Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity. Dis. Model Mech. 9, 823–838 (2016).
pubmed: 27491084
pmcid: 5007983
doi: 10.1242/dmm.024703
Kohanski, M. A., Dwyer, D. J., Wierzbowski, J., Cottarel, G. & Collins, J. J. Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death. Cell 135, 679–690 (2008).
pubmed: 19013277
pmcid: 2684502
doi: 10.1016/j.cell.2008.09.038
Oishi, N. et al. XBP1 mitigates aminoglycoside-induced endoplasmic reticulum stress and neuronal cell death. Cell Death Dis. 6, e1763 (2015).
pubmed: 25973683
pmcid: 4669688
doi: 10.1038/cddis.2015.108
Peric, M. et al. Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan. Sci. Rep. 6, 28751 (2016).
pubmed: 27346163
pmcid: 4921836
doi: 10.1038/srep28751
Lee, H. & Yoon, Y. Mitochondrial fission: regulation and ER connection. Mol. Cells 37, 89–94 (2014).
pubmed: 24598992
pmcid: 3935634
doi: 10.14348/molcells.2014.2329
Yu, T., Jhun, B. S. & Yoon, Y. High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission. Antioxid. Redox Signal 14, 425–437 (2011).
pubmed: 20518702
pmcid: 3025178
doi: 10.1089/ars.2010.3284
Seervi, M., Joseph, J., Sobhan, P. K., Bhavya, B. C. & Santhoshkumar, T. R. Essential requirement of cytochrome c release for caspase activation by procaspase-activating compound defined by cellular models. Cell Death Dis. 2, e207 (2011).
pubmed: 21900958
pmcid: 3186908
doi: 10.1038/cddis.2011.90
Anderson, G. R. et al. Dysregulation of mitochondrial dynamics proteins are a targetable feature of human tumors. Nat. Commun. 9, 1677 (2018).
pubmed: 29700304
pmcid: 5919970
doi: 10.1038/s41467-018-04033-x
Haroon, S. & Vermulst, M. Linking mitochondrial dynamics to mitochondrial protein quality control. Curr. Opin. Genet Dev. 38, 68–74 (2016).
pubmed: 27235806
doi: 10.1016/j.gde.2016.04.004
Sano, R. & Reed, J. C. ER stress-induced cell death mechanisms. Biochim Biophys. Acta 1833, 3460–3470 (2013).
pubmed: 23850759
doi: 10.1016/j.bbamcr.2013.06.028
Verfaillie, T. et al. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ. 19, 1880–1891 (2012).
pubmed: 22705852
pmcid: 3469056
doi: 10.1038/cdd.2012.74
Yan, M., Shu, S., Guo, C., Tang, C. & Dong, Z. Endoplasmic reticulum stress in ischemic and nephrotoxic acute kidney injury. Ann. Med. 50, 381–390 (2018).
pubmed: 29895209
pmcid: 6333465
doi: 10.1080/07853890.2018.1489142
Wang, Z. et al. Nucleophosmin, a critical Bax cofactor in ischemia-induced cell death. Mol. Cell Biol. 33, 1916–1924 (2013).
pubmed: 23459946
pmcid: 3647959
doi: 10.1128/MCB.00015-13
Pierson-Marchandise, M. et al. The drugs that mostly frequently induce acute kidney injury: a case—non-case study of a pharmacovigilance database. Br. J. Clin. Pharm. https://doi.org/10.1111/bcp.13216 (2016).
doi: 10.1111/bcp.13216
Beane, W. S., Morokuma, J., Adams, D. S. & Levin, M. A chemical genetics approach reveals H,K-ATPase-mediated membrane voltage is required for planarian head regeneration. Chem. Biol. 18, 77–89 (2011).
pubmed: 21276941
pmcid: 3278711
doi: 10.1016/j.chembiol.2010.11.012
Cancer Genome Atlas Research, N. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543–550 (2014).
doi: 10.1038/nature13385
Tantama, M., Martinez-Francois, J. R., Mongeon, R. & Yellen, G. Imaging energy status in live cells with a fluorescent biosensor of the intracellular ATP-to-ADP ratio. Nat. Commun. 4, 2550 (2013).
pubmed: 24096541
pmcid: 3852917
doi: 10.1038/ncomms3550
Belousov, V. V. et al. Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nat. Methods 3, 281–286 (2006).
pubmed: 16554833
doi: 10.1038/nmeth866
Dagda, R. K. et al. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J. Biol. Chem. 284, 13843–13855 (2009).
pubmed: 19279012
pmcid: 2679485
doi: 10.1074/jbc.M808515200
Dunn, K. W., Kamocka, M. M. & McDonald, J. H. A practical guide to evaluating colocalization in biological microscopy. Am. J. Physiol. Cell Physiol. 300, C723–C742 (2011).
pubmed: 21209361
pmcid: 3074624
doi: 10.1152/ajpcell.00462.2010
Corbeski, I. et al. Microscale thermophoresis analysis of chromatin interactions. Methods Mol. Biol. 1837, 177–197 (2018).
pubmed: 30109612
doi: 10.1007/978-1-4939-8675-0_11
Lazarev, V. F. et al. Sensitizing tumor cells to conventional drugs: HSP70 chaperone inhibitors, their selection and application in cancer models. Cell Death Dis. 9, 41 (2018).
pubmed: 29348557
pmcid: 5833849
doi: 10.1038/s41419-017-0160-y
Berlett, B. S. & Stadtman, E. R. Protein oxidation in aging, disease, and oxidative stress. J. Biol. Chem. 272, 20313–20316 (1997).
pubmed: 9252331
doi: 10.1074/jbc.272.33.20313
Huiting, L. N. et al. UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response. Leukemia 32, 2339–2351 (2018).
pubmed: 29743725
pmcid: 6202254
doi: 10.1038/s41375-018-0141-x
Beriault, D. R. & Werstuck, G. H. Detection and quantification of endoplasmic reticulum stress in living cells using the fluorescent compound, Thioflavin T. Biochim Biophys. Acta 1833, 2293–2301 (2013).
pubmed: 23747341
doi: 10.1016/j.bbamcr.2013.05.020
Shashar, M. et al. Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk. Sci. Transl. Med. 9, https://doi.org/10.1126/scitranslmed.aam8475 (2017).
Sanchez-Alvarez, M., Del Pozo, M. A. & Bakal, C. AKT-mTOR signaling modulates the dynamics of IRE1 RNAse activity by regulating ER-mitochondria contacts. Sci. Rep. 7, 16497 (2017).
pubmed: 29184100
pmcid: 5705697
doi: 10.1038/s41598-017-16662-1
Shcherbakov, D. et al. Ribosomal mistranslation leads to silencing of the unfolded protein response and increased mitochondrial biogenesis. Commun. Biol. 2, 381 (2019).
pubmed: 31637312
pmcid: 6797716
doi: 10.1038/s42003-019-0626-9
Wang, Z. et al. Induction of heat shock protein 70 inhibits ischemic renal injury. Kidney Int. 79, 861–870 (2011).
pubmed: 21270764
doi: 10.1038/ki.2010.527
pmcid: 21270764
Bonora, M. et al. ATP synthesis and storage. Purinergic Signal 8, 343–357 (2012).
pubmed: 22528680
pmcid: 3360099
doi: 10.1007/s11302-012-9305-8
Ivashchenko, O. et al. Intraperoxisomal redox balance in mammalian cells: oxidative stress and interorganellar cross-talk. Mol. Biol. Cell 22, 1440–1451 (2011).
pubmed: 21372177
pmcid: 3084667
doi: 10.1091/mbc.e10-11-0919
Kabakov, A. E., Budagova, K. R., Latchman, D. S. & Kampinga, H. H. Stressful preconditioning and HSP70 overexpression attenuate proteotoxicity of cellular ATP depletion. Am. J. Physiol. Cell Physiol. 283, C521–C534 (2002).
pubmed: 12107062
doi: 10.1152/ajpcell.00503.2001
Nollen, E. A., Brunsting, J. F., Song, J., Kampinga, H. H. & Morimoto, R. I. Bag1 functions in vivo as a negative regulator of Hsp70 chaperone activity. Mol. Cell Biol. 20, 1083–1088 (2000).
pubmed: 10629065
pmcid: 85225
doi: 10.1128/MCB.20.3.1083-1088.2000
Brooks, C., Wei, Q., Cho, S. G. & Dong, Z. Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. J. Clin. Invest. 119, 1275–1285 (2009).
pubmed: 19349686
pmcid: 2673870
doi: 10.1172/JCI37829
Marchi, S., Patergnani, S. & Pinton, P. The endoplasmic reticulum-mitochondria connection: one touch, multiple functions. Biochim. Biophys. Acta 1837, 461–469 (2014).
pubmed: 24211533
doi: 10.1016/j.bbabio.2013.10.015
Armstrong, J. A. et al. Oxidative stress alters mitochondrial bioenergetics and modifies pancreatic cell death independently of cyclophilin D, resulting in an apoptosis-to-necrosis shift. J. Biol. Chem. 293, 8032–8047 (2018).
pubmed: 29626097
pmcid: 5971444
doi: 10.1074/jbc.RA118.003200
Shang, F. & Taylor, A. Ubiquitin-proteasome pathway and cellular responses to oxidative stress. Free Radic. Biol. Med. 51, 5–16 (2011).
pubmed: 21530648
pmcid: 3109097
doi: 10.1016/j.freeradbiomed.2011.03.031
Higgins, R. et al. The unfolded protein response triggers site-specific regulatory ubiquitylation of 40S ribosomal proteins. Mol. Cell 59, 35–49 (2015).
pubmed: 26051182
pmcid: 4491043
doi: 10.1016/j.molcel.2015.04.026
Rao, R. V. & Bredesen, D. E. Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr. Opin. Cell Biol. 16, 653–662 (2004).
pubmed: 15530777
pmcid: 3970707
doi: 10.1016/j.ceb.2004.09.012
Chen, L. et al. Cab45S inhibits the ER stress-induced IRE1-JNK pathway and apoptosis via GRP78/BiP. Cell Death Dis. 5, e1219 (2014).
pubmed: 24810055
pmcid: 4047922
doi: 10.1038/cddis.2014.193
Rivas, A., Vidal, R. L. & Hetz, C. Targeting the unfolded protein response for disease intervention. Expert Opin. Ther. Targets 19, 1203–1218 (2015).
pubmed: 26166159
doi: 10.1517/14728222.2015.1053869
Hong, F. et al. CNPY2 is a key initiator of the PERK-CHOP pathway of the unfolded protein response. Nat. Struct. Mol. Biol. 24, 834–839 (2017).
pubmed: 28869608
pmcid: 6102046
doi: 10.1038/nsmb.3458
Lin, J. H. et al. IRE1 signaling affects cell fate during the unfolded protein response. Science 318, 944–949 (2007).
pubmed: 17991856
pmcid: 3670588
doi: 10.1126/science.1146361
Wang, H. et al. Tunicamycin-induced unfolded protein response in the developing mouse brain. Toxicol. Appl. Pharm. 283, 157–167 (2015).
doi: 10.1016/j.taap.2014.12.019
Hu, H., Tian, M., Ding, C. & Yu, S. The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection. Front Immunol. 9, 3083 (2018).
pubmed: 30662442
doi: 10.3389/fimmu.2018.03083
Michaeloudes, C., Bhavsar, P. K., Mumby, S., Chung, K. F. & Adcock, I. M. Dealing with stress: defective metabolic adaptation in chronic obstructive pulmonary disease pathogenesis. Ann. Am. Thorac. Soc. 14, S374–S382 (2017).
pubmed: 29161091
pmcid: 5711272
doi: 10.1513/AnnalsATS.201702-153AW
Pihan, P., Carreras-Sureda, A. & Hetz, C. BCL-2 family: integrating stress responses at the ER to control cell demise. Cell Death Differ. 24, 1478–1487 (2017).
pubmed: 28622296
pmcid: 5563989
doi: 10.1038/cdd.2017.82
Sassano, M. L., van Vliet, A. R. & Agostinis, P. Mitochondria-associated membranes as networking platforms and regulators of cancer cell fate. Front Oncol. 7, 174 (2017).
pubmed: 28868254
pmcid: 5563315
doi: 10.3389/fonc.2017.00174
Bansal, S., Biswas, G. & Avadhani, N. G. Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity. Redox Biol. 2, 273–283 (2014).
pubmed: 24494190
doi: 10.1016/j.redox.2013.07.004
Tilokani, L., Nagashima, S., Paupe, V. & Prudent, J. Mitochondrial dynamics: overview of molecular mechanisms. Essays Biochem. 62, 341–360 (2018).
pubmed: 30030364
pmcid: 6056715
doi: 10.1042/EBC20170104
Iqbal, S. & Hood, D. A. Oxidative stress-induced mitochondrial fragmentation and movement in skeletal muscle myoblasts. Am. J. Physiol. Cell Physiol. 306, C1176–C1183 (2014).
pubmed: 24740540
pmcid: 4059998
doi: 10.1152/ajpcell.00017.2014
Li, T. et al. GOLPH3 mediated Golgi stress response in modulating N2A cell death upon oxygen-glucose deprivation and reoxygenation injury. Mol. Neurobiol. 53, 1377–1385 (2016).
pubmed: 25633094
doi: 10.1007/s12035-014-9083-0
Cooper, J. F. et al. Activation of the mitochondrial unfolded protein response promotes longevity and dopamine neuron survival in Parkinson’s disease models. Sci. Rep. 7, 16441 (2017).
pubmed: 29180793
pmcid: 5703891
doi: 10.1038/s41598-017-16637-2
Favaro, G. et al. DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass. Nat. Commun. 10, 2576 (2019).
pubmed: 31189900
pmcid: 6561930
doi: 10.1038/s41467-019-10226-9
Lebeau, J. et al. The PERK arm of the unfolded protein response regulates mitochondrial morphology during acute endoplasmic reticulum stress. Cell Rep. 22, 2827–2836 (2018).
pubmed: 29539413
pmcid: 5870888
doi: 10.1016/j.celrep.2018.02.055
Bhargava, A. et al. Ultrafine particulate matter impairs mitochondrial redox homeostasis and activates phosphatidylinositol 3-kinase mediated DNA damage responses in lymphocytes. Environ. Pollut. 234, 406–419 (2018).
pubmed: 29202419
doi: 10.1016/j.envpol.2017.11.093
Youle, R. J. & van der Bliek, A. M. Mitochondrial fission, fusion, and stress. Science 337, 1062–1065 (2012).
pubmed: 22936770
pmcid: 4762028
doi: 10.1126/science.1219855
Chui, M. H. et al. Chromosomal instability and mTORC1 activation through PTEN loss contribute to proteotoxic stress in ovarian carcinoma. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-18-3029 (2019).
doi: 10.1158/0008-5472.CAN-18-3029
pubmed: 31530568
Yang, M. et al. Sirtuin 2 expression suppresses oxidative stress and senescence of nucleus pulposus cells through inhibition of the p53/p21 pathway. Biochem. Biophys. Res. Commun. 513, 616–622 (2019).
pubmed: 30981502
doi: 10.1016/j.bbrc.2019.03.200
Szabadkai, G. et al. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca
pubmed: 17178908
pmcid: 2064700
doi: 10.1083/jcb.200608073
Sorrentino, V. et al. Enhancing mitochondrial proteostasis reduces amyloid-beta proteotoxicity. Nature 552, 187–193 (2017).
pubmed: 29211722
pmcid: 5730497
doi: 10.1038/nature25143
Lumley, E. C. et al. Moderate endoplasmic reticulum stress activates a PERK and p38-dependent apoptosis. Cell Stress Chaperones 22, 43–54 (2017).
pubmed: 27761878
doi: 10.1007/s12192-016-0740-2
Walter, P. & Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081–1086 (2011).
pubmed: 22116877
doi: 10.1126/science.1209038
Kim, R., Emi, M., Tanabe, K. & Murakami, S. Role of the unfolded protein response in cell death. Apoptosis 11, 5–13 (2006).
pubmed: 16374548
doi: 10.1007/s10495-005-3088-0
Gotoh, T., Terada, K., Oyadomari, S. & Mori, M. hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death Differ. 11, 390–402 (2004).
pubmed: 14752510
doi: 10.1038/sj.cdd.4401369
Wilkinson, K. A. & Henley, J. M. Mechanisms, regulation and consequences of protein SUMOylation. Biochem. J. 428, 133–145 (2010).
pubmed: 20462400
pmcid: 3310159
doi: 10.1042/BJ20100158
Molinari, M., Galli, C., Piccaluga, V., Pieren, M. & Paganetti, P. Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ER. J. Cell Biol. 158, 247–257 (2002).
pubmed: 12119363
pmcid: 2173128
doi: 10.1083/jcb.200204122
Zhang, K. & Kaufman, R. J. Kaufman, Protein folding in the endoplasmic reticulum and the unfolded protein response. Handb Exp Pharmacol. 69–91 (2006).
Sun, S. Y. et al. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res. 65, 7052–7058 (2005).
pubmed: 16103051
doi: 10.1158/0008-5472.CAN-05-0917
Cui, J. et al. Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models. Sci Rep. 5, 11256 (2015).
pubmed: 26052900
pmcid: 4459224
doi: 10.1038/srep11256
Ramachandiran, S. et al. Mitogen-activated protein kinases contribute to reactive oxygen species-induced cell death in renal proximal tubule epithelial cells. Chem Res Toxicol 15, 1635–1642 (2002).
pubmed: 12482247
doi: 10.1021/tx0200663
Park, K. M., Chen, A. & Bonventre, J. V. Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem. 276, 11870–11876 (2001).
pubmed: 11150293
doi: 10.1074/jbc.M007518200
Papadakis, E. S. et al. The regulation of Bax by c-Jun N-terminal protein kinase (JNK) is a prerequisite to the mitochondrial-induced apoptotic pathway. FEBS Lett. 580, 1320–1326 (2006).
pubmed: 16458303
doi: 10.1016/j.febslet.2006.01.053
Trinei, M. et al. A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21, 3872–3878 (2002).
pubmed: 12032825
doi: 10.1038/sj.onc.1205513
Berns, K. et al. A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428, 431–437 (2004).
pubmed: 15042092
doi: 10.1038/nature02371
Nisoli, E. et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310, 314–317 (2005).
pubmed: 16224023
doi: 10.1126/science.1117728
Lopez-Novoa, J. M. et al. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 79, 33–45 (2011).
pubmed: 20861826
doi: 10.1038/ki.2010.337
Ling, H. et al. Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice. Am J Physiol. 277, F383–F390 (1999).
pubmed: 10484522
Casanova, A. G. et al. Key role of oxidative stress in animal models of aminoglycoside nephrotoxicity revealed by a systematic analysis of the antioxidant-to-nephroprotective correlation. Toxicology 385, 10–17 (2017).
pubmed: 28472626
doi: 10.1016/j.tox.2017.04.015
Moreira, M. A. et al. Ascorbic acid reduces gentamicin-induced nephrotoxicity in rats through the control of reactive oxygen species. Clin Nutr. 33, 296–301 (2014).
pubmed: 23810398
doi: 10.1016/j.clnu.2013.05.005
Hetz, C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 13, 89–102 (2012).
pubmed: 22251901
doi: 10.1038/nrm3270
Guo, C. et al. SUMOylation occurs in acute kidney injury and plays a cytoprotective role. Biochim Biophys Acta. 1852, 482–489 (2015).
pubmed: 25533125
doi: 10.1016/j.bbadis.2014.12.013
Czubryt, M. P. et al. Regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) and mitochondrial function by MEF2 and HDAC5. Proc Natl Acad Sci USA. 100, 1711–1716 (2003).
pubmed: 12578979
doi: 10.1073/pnas.0337639100
Puigserver, P. & Spiegelman, B. M. Spiegelman, Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev. 24, 78–90 (2003).
pubmed: 12588810
doi: 10.1210/er.2002-0012