#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Efficacy of a mitochondrion-targeting agent for reducing the level of urinary protein in rats with puromycin aminonucleoside-induced minimal-change nephrotic syndrome


Autoři: Yuko Fujii aff001;  Hideki Matsumura aff001;  Satoshi Yamazaki aff001;  Akihiko Shirasu aff002;  Hyogo Nakakura aff003;  Tohru Ogihara aff001;  Akira Ashida aff001
Působiště autorů: Department of Pediatrics, Osaka Medical College, Takatsuki, Osaka, Japan aff001;  Department of Pediatrics, Hirakata City Hospital, Hirakata, Osaka, Japan aff002;  Department of Hemodialysis and Apheresis, Arisawa General Hospital, Hirakata, Osaka, Japan aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227414

Souhrn

Background

Oxidative stress is a major factor responsible for minimal-change nephrotic syndrome (MCNS), which occurs most commonly in children. However, the influence of oxidative stress localized to mitochondria remains unclear. We examined the effect of a mitochondrion-targeting antioxidant, MitoTEMPO, in rats with puromycin aminonucleoside (PAN)-induced MCNS to clarify the degree to which mitochondrial oxidative stress affects MCNS.

Materials and methods

Thirty Wistar rats were divided into three groups: normal saline group (n = 7), PAN group (n = 12), and PAN + MitoTEMPO group (n = 11). Rats in the PAN and PAN + MitoTEMPO groups received PAN on day 1, and those in the PAN + MitoTEMPO group received MitoTEMPO on days 0 to 9. Whole-day urine samples were collected on days 3 and 9, and samples of glomeruli and blood were taken for measurement of lipid peroxidation products. We also estimated the mitochondrial damage score in podocytes in all 3 groups using electron microscopy.

Results

Urinary protein excretion on day 9 and the levels of lipid peroxidation products in urine, glomeruli, and blood were significantly lower in the PAN + MitoTEMPO group than in the PAN group (p = 0.0019, p = 0.011, p = 0.039, p = 0.030). The mitochondrial damage score in podocytes was significantly lower in the PAN + MitoTEMPO group than in the PAN group (p <0.0001).

Conclusions

This mitochondrion-targeting agent was shown to reduce oxidative stress and mitochondrial damage in a MCNS model. A radical scavenger targeting mitochondria could be a promising drug for treatment of MCNS.

Klíčová slova:

Electron microscopy – Ethanol – Excretion – Glomeruli – Kidneys – Mitochondria – Oxidative stress – Urine


Zdroje

1. Picone P, Nuzzo D, Caruana L, Scafidi V, Di Carlo M. Mitochondrial dysfunction: different routes to Alzheimer’s disease therapy. Oxid Med Cell Longev. 2014;2014: 780179. doi: 10.1155/2014/780179 25221640

2. Ni R, Cao T, Xiong S, Ma J, Fan GC, Lacefield JC, et al. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy. Free Radic Biol Med 2016;90: 12–23. doi: 10.1016/j.freeradbiomed.2015.11.013 26577173

3. Lee SJ, Ryter SW, Xu JF, Nakahira K, Kim HP, Choi AM, et al. Carbon monoxide activates autophagy via mitochondrial reactive oxygen species formation. Am J Respir Cell Mol Biol 2011;45: 867–873. doi: 10.1165/rcmb.2010-0352OC 21441382

4. Novak EA, Mollen KP. Mitochondrial dysfunction in inflammatory bowel disease. Front Cell Dev Biol 2015;3: 62. doi: 10.3389/fcell.2015.00062 26484345

5. Qian T, Nieminen AL, Herman B, Lemasters JJ. Mitochondrial permeability transition in pH-dependent reperfusion injury to rat hepatocytes. Am J Physiol 1997;273: C1783–1792. doi: 10.1152/ajpcell.1997.273.6.C1783 9435481

6. Dong LF, Neuzil J. Mitochondria in cancer: why mitochondria are a good target for cancer therapy. Prog Mol Biol Transl Sci. 2014;127: 211–227. doi: 10.1016/B978-0-12-394625-6.00008-8 25149219

7. Patil NK, Parajuli N, MacMillan-Crow LA, Mayeux PR. Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury. Am J Physiol Renal Physiol. 2014;306: F734–743. doi: 10.1152/ajprenal.00643.2013 24500690

8. Cui J, Bai XY, Sun X, Cai G, Hong Q, Ding R, et al. Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models. Sci Rep 2015;5: 11256. doi: 10.1038/srep11256 26052900

9. Lin CH, Chang LW, Wei YH, Wu SB, Yang CS, Chang WH, et al. Electronic microscopy evidence for mitochondria as targets for Cd/Se/Te-based quantum dot 705 toxicity in vivo. Kaohsiung J Med Sci. 2012;28: S53–62. doi: 10.1016/j.kjms.2012.05.011 22871604

10. Zhu C, Huang S, Yuan Y, Ding G, Chen R, Liu B, et al. Mitochondrial dysfunction mediates aldosterone-induced podocyte damage: a therapeutic target of PPARγ. Am J Pathol. 2011;178: 2020–2031. doi: 10.1016/j.ajpath.2011.01.029 21514419

11. Holthöfer H, Kretzler M, Haltia A, Solin ML, Taanman JW, Schägger H, et al. Altered gene expression and functions of mitochondria in human nephrotic syndrome. FASEB J. 1999;13: 523–532. doi: 10.1096/fasebj.13.3.523 10064619

12. Che R, Zhu C, Ding G, Zhao M, Bai M, Jia Z, et al. Huaier cream protects against adriamycin-induced nephropathy by restoring mitochondrial function via PGC-1α upregulation. PPAR Res. 2015;2015: 720383. doi: 10.1155/2015/720383 25861251

13. Emma F, Montini G, Parikh SM, Salviati L. Mitochondrial dysfunction in inherited renal disease and acute kidney injury. Nat Rev Nephrol. 2016;12: 267–280. doi: 10.1038/nrneph.2015.214 26804019

14. Guan N, Ren YL, Liu XY, Zhang Y, Pei P, Zhu SN, et al. Protective role of cyclosporine A and minocycline on mitochondrial disequilibrium-related podocyte injury and proteinuria occurrence induced by adriamycin. Nephrol Dial Transplant. 2015;30: 957–969. doi: 10.1093/ndt/gfv015 25646018

15. Hotta O, Inoue CN, Miyabayashi S, Furuta T, Takeuchi A, Taguma Y. Clinical and pathologic features of focal segmental glomerulosclerosis with mitochondrial tRNALeu(UUR) gene mutation. Kidney Int. 2001;59: 1236–1243. doi: 10.1046/j.1523-1755.2001.0590041236.x 11260383

16. Czajka A, Ajaz S, Gnudi L, Parsade CK, Jones P, Reid F, et al. Altered mitochondrial function, mitochondrial DNA and reduced metabolic flexibility in patients with diabetic nephropathy. EBioMedicine. 2015;2: 499–512. doi: 10.1016/j.ebiom.2015.04.002 26288815

17. Szabolcs MJ, Seigle R, Shanske S, Bonilla E, DiMauro S, D'Agati V. Mitochondrial DNA deletion: a cause of chronic tubulointerstitial nephropathy. Kidney Int. 1994; 45: 1388–1396. doi: 10.1038/ki.1994.181 8072250

18. Granata S, Dalla Gassa A, Tomei P, Lupo A, Zaza G. Mitochondria: a new therapeutic target in chronic kidney disease. Nutr Metab (Lond.) 2015;12: 49.

19. Kezic A, Spasojevic I, Lezaic V, Bajcetic M. Mitochondria-targeted antioxidants: Future perspectives in kidney ischemia-reperfusion injury. Oxid Med Cell Longev. 2016;2016: 2950503. doi: 10.1155/2016/2950503 27313826

20. Papazova DA, Friederich-Persson M, Joles JA, Verhaar MC. Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension. Am J Physiol Renal Physiol. 2015;308: F22–28. doi: 10.1152/ajprenal.00278.2014 25275014

21. Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, et al. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res. 2010; 107: 106–116. doi: 10.1161/CIRCRESAHA.109.214601 20448215

22. Rocha VC, França LS, de Araújo CF, Ng AM, de Andrade CM, Andrade AC, et al. Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice. Cancer Chemother Pharmacol. 2016;77: 659–662. doi: 10.1007/s00280-015-2949-7 26712129

23. Dikalov S. Cross talk between mitochondria and NADPH oxidases. Free Radic Biol Med. 2011;51: 1289–1301. doi: 10.1016/j.freeradbiomed.2011.06.033 21777669

24. Ademowo OS, Dias HKI, Burton DGA, Griffiths HR. Lipid (per) oxidation in mitochondria: an emerging target in the ageing process? Biogerontology 2017;18: 859–879. doi: 10.1007/s10522-017-9710-z 28540446

25. Gwinner W, Landmesser U, Brandes RP, Kubat B, Plasger J, Eberhard O, et al. Reactive oxygen species and antioxidant defense in puromycin aminonucleoside glomerulopathy. J Am Soc Nephrol. 1997;8: 1722–1731. 9355075

26. Vega-Warner V, Ransom RF, Vincent AM, Brosius FC, Smoyer WE. Induction of antioxidant enzymes in murine podocytes precedes injury by puromycin aminonucleoside. Kidney Int. 2004;66: 1881–1889. doi: 10.1111/j.1523-1755.2004.00962.x 15496159

27. Nakakura H, Ashida A, Hirano K, Tamai H. Oxidative stress in a rat model of nephrosis can be quantified by electron spin resonance. Pediatr Nephrol 2004;19: 266–270. doi: 10.1007/s00467-003-1332-9 14714169

28. Matsumura H, Ashida A, Hirano K, Nakakura H, Tamai H. Protective effect of radical scavenger edaravone against puromycin nephrosis. Clin Nephrol. 2006;66: 405–410. doi: 10.5414/cnp66405 17176911

29. Takayasu Y, Nakaki J, Kawasaki T, Koda K, Ago Y, Baba A, et al. Edaravone, a radical scavenger, inhibits mitochondrial permeability transition pore in rat brain. J Pharmacol Sci. 2007;103: 434–437. doi: 10.1254/jphs.sc0070014 17409627

30. Zhang ZW, Xu XC, Liu T, Yuan S. Mitochondrion-permeable antioxidants to treat ROS-burst-mediated acute diseases. Oxid Med Cell Longev. 2016;2016: 6859523. doi: 10.1155/2016/6859523 26649144

31. Shen X, Jiang H, Ying M, Xie Z, Li X, Wang H, et al. Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models. Sci Rep. 2016;6: 32087. doi: 10.1038/srep32087 27580845

32. Li X, Tao H, Xie K, Ni Z, Yan Y, Wei K, et al. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion. PLoS One 2014;9: e92003. doi: 10.1371/journal.pone.0092003 24642777

33. Hasegawa M, Ogihara T, Tamai H, Hiroi M. Hypothermic inhibition of apoptotic pathways for combined neurotoxicity of iron and ascorbic acid in differentiated PC12 cells: reduction of oxidative stress and maintenance of the glutathione redox state. Brain Res. 2009;1283: 1–13. doi: 10.1016/j.brainres.2009.06.016 19524561

34. Sesso A, Belizário JE, Marques MM, Higuchi ML, Schumacher RI, Colquhoun A, et al. Mitochondrial swelling and incipient outer membrane rupture in preapoptotic and apoptotic cells. Anat Rec. (Hoboken) 2012;295: 1647–1659.

35. Sweetwyne MT, Pippin JW, Eng DG, Hudkins KL, Chiao YA, Campbell MD, et al. The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age. Kidney Int. 2017;91: 1126–1145. doi: 10.1016/j.kint.2016.10.036 28063595

36. Picard M, Shirihai OS, Gentil BJ, Burelle Y. Mitochondrial morphology transitions and functions: implications for retrograde signaling? Am J Physiol Regul Integr Comp. Physiol. 2013;304: R393–406. doi: 10.1152/ajpregu.00584.2012 23364527

37. Gunter TE, Yule DI, Gunter KK, Eliseev RA, Salter JD. Calcium and mitochondria. FEBS Lett. 2004;567: 96–102. doi: 10.1016/j.febslet.2004.03.071 15165900

38. Gunter TE, Sheu SS. Characteristics and possible functions of mitochondrial Ca2+ transport mechanisms. Biochim Biophys Acta. 2009;1787: 1291–1308. doi: 10.1016/j.bbabio.2008.12.011 19161975

39. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROS-induced ROS release: An update and review. Biochim Biophys Acta. 2006;1757: 509–517. doi: 10.1016/j.bbabio.2006.04.029 16829228

40. Aon MA, Cortassa S, Akar FG, O'Rourke B. Mitochondrial criticality: a new concept at the turning point of life or death. Biochim Biophys Acta 2006;1762: 232–240. doi: 10.1016/j.bbadis.2005.06.008 16242921

41. Siemen D, Ziemer M. What is the nature of the mitochondrial permeability transition pore and what is it not? IUBMB Life 2013;65: 255–262. doi: 10.1002/iub.1130 23341030


Článek vyšel v časopise

PLOS One


2020 Číslo 1
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#