A Thermolabile Aldolase A Mutant Causes Fever-Induced Recurrent Rhabdomyolysis without Hemolytic Anemia

English version České info

Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease.

Vyšlo v časopise: A Thermolabile Aldolase A Mutant Causes Fever-Induced Recurrent Rhabdomyolysis without Hemolytic Anemia. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004711
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004711

Souhrn

Zdroje

1. LaforetP, Vianey-SabanC (2010) Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges. Neuromuscul Disord 20 : 693–700.

2. DiMauroS, GaroneC, NainiA (2010) Metabolic myopathies. Curr Rheumatoly Rep 12 : 386–393.

3. TeinI, DiMauroS, DeVivoDC (1990) Recurrent childhood myoglobinuria. Adv Pediatr 37 : 77–117.

4. ZehariaA, ShaagA, HoutkooperRH, HindiT, de LonlayP, et al. (2008) Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood. Am J Hum Genet 83 : 489–494.

5. Michot C, Hubert L, Brivet M, De Meirleir L, Valayannopoulos V, et al. (2010 LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood. Hum Mutat 31: E1564–1573.

6. MichotC, HubertL, RomeroNB, GoudaA, MamouneA, et al. (2012) Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercice-induced myalgia. J Inherit Metab Dis 35(6): 1119–1128.

7. ToninP, LewisP, ServideiS, DiMauroS (1990) Metabolic causes of myoglobinuria. AnnNeurol 27 : 181–185.

8. OhkumaA, NoguchiS, MalicdanMC, FukudaT, et al. (2009) Clinical and genetic analysis of lipid storage myopathies. Muscle Nerve 39 : 333–342.

9. YaoDC, TolanDR, MurrayMF, HarrisDJ, DarrasBT, et al. (2004) Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr). Blood 103 : 2401–2403.

10. ChenCW, LinJ, ChuYW (2013) iStable: off-the-shelf predictor integration for predicting protein stability changes. BMC Bioinformatics 14 Suppl 2S5.

11. TakahashiI, TakasakiY, HoriK (1989) Site-directed mutagenesis of human aldolase isozymes: the role of Cys-72 and Cys-338 residues of aldolase A and of the carboxy-terminal Tyr residues of aldolases A and B. J Biochem. 105 : 281–286.

12. van AdelBA, TarnopolskyMA (2009) Metabolic myopathies: update 2009. J Clin Neuromuscul Dis 10 : 97–121.

13. KreuderJ, BorkhardtA, ReppR, PekrunA, GottscheB, et al. (1996) Brief report: inherited metabolic myopathy and hemolysis due to a mutation in aldolase A. N Engl J Med. 334 : 1100–1104.

14. MiwaS, FujiiH, TaniK, TakahashiK, TakegawaS, et al. (1981) Two cases of red cell aldolase deficiency associated with hereditary hemolytic anemia in a Japanese family. Am J Hematol 11 : 425–437.

15. BeutlerE, ScottS, BishopA, MargolisN, MatsumotoF, et al. (1973) Red cell aldolase deficiency and hemolytic anemia: a new syndrome. Trans Assoc Am Physicians 86 : 154–166.

16. KishiH, MukaiT, HironoA, FujiiH, MiwaS, et al. (1987) Human aldolase A deficiency associated with a hemolytic anemia: thermolabile aldolase due to a single base mutation. ProcNatl Acad Sci U S A 84 : 8623–8627.

17. PachecoP, Vieira-de-AbreuA, GomesRN, Barbosa-LimaG, WermelingerLB, et al. (2007) Monocyte chemoattractant protein-1/CC chemokine ligand 2 controls microtubule-driven biogenesis and leukotriene B4-synthesizing function of macrophage lipid bodies elicited by innate immune response. J Immunol 179 : 8500–8508.

18. GomesRN, FiguieredoRT, BozzaFA, PachecoP, AmancioRT, et al. (2006) Increased susceptibility to septic and endotoxic shock in monocyte chemoattractant protein 1/cc chemokine ligand 2-defiient mice correlates with reduced interleukin 10 and enhanced macrophage migration inhibitory factor production. Shock 26 : 457–463.

19. FareseRVJr, WalterTC (2009) Lipid droplets finally get a little R-E-S-P-E-C-T. Cell 139 : 855–860.

20. BeerninkPT, TolanDR (1994) Subunit interface mutants of rabbit muscle aldolase form active dimers. Protein Sci 3 : 1383–1391.

21. TsantesAE, BonovasS, TravlouA, SitarasNM (2006) Redox imbalance, macrocytosis, and RBC homeostasis. Antioxid Redox Signal 8 : 1205–1216.

22. MarinkovicD, ZhangX, YalcinS, LucianoJP, BrugnaraC, et al. (2007) Foxo3 is required for the regulation of oxidative stress in erythropoiesis. J Clin Invest 117 : 2133–2144.

23. MatesJM, Perez-GomezC, OlallaL, SeguraJM, BlancaM (2000) Allergy to drugs: antioxidant enzymic activities, lipid peroxidation and protein oxidative damage in human blood. Cell Biochem Funct 18 : 77–84.

24. CrawfordJH, IsbellTS, HuangZ, ShivaS, ChackoBK, et al. (2006) Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 107 : 566–574.

25. BerendseK, EbberinkMS, IjlstL, Poll-TheBT, WandersRJ, et al. (2013) Arginine improves peroxisome functioning in cells from patients with a mild peroxisome biogenesis disorder. Orphanet J Rare Dis 8 : 138.

26. RothSD, SchuttrumpfJ, MilanovP, AbrissD, UngererC, et al. (2012) Chemical chaperones improve protein secretion and rescue mutant factor VIII in mice with hemophilia A. PLoS One. 7: e44505.

27. SenesiP, LuziL, MontesanoA, MazzocchiN, TerruzziI (2013) Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation. J Transl Med 11 : 174.

28. WenH, TingJP, O'NeillLA (2012) A role for the NLRP3 inflammasome in metabolic diseases—did Warburg miss inflammation? Nat Immunol 13 : 352–357.

29. ArendWP, PalmerG, GabayC (2008) IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev 223 : 20–38.

30. KrawczykCM, HolowkaT, SunJ, BlagihJ, AmielE, et al. (2010) Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115 : 4742–4749.

31. MaedlerK, SergeevP, RisF, OberholzerJ, Joller-JemelkaHI, et al. (2002) Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110 : 851–860.

32. FeingoldKR, MoserA, PatzekSM, ShigenagaJK, GrunfeldC (2009) Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm. J Lipid Res 50 : 2055–2063.

33. BarronJT, KoppSJ, TowJ, ParrilloJE (1994) Fatty acid, tricarboxylic acid cycle metabolites, and energy metabolism in vascular smoth muscle. Am J Physiol 267: H764–769.

34. SharmaS, AdrogueJV, GolfmanL, UrayI, LemmJ, et al. (2004) Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J 18 : 1692–1700.

35. VissingJ, HallerRG (2012) Mechanisms of exertional fatigue in muscle glycogenoses. Neuromuscul Disord 22 Suppl 3S168–171.

36. WaingehVF, GustafsonCD, KozliakEI, LoweSL, KnullHR, et al. (2006) Glycolytic enzyme interactions with yeast and skeletal muscle F-actin. Biophys J 90 : 1371–1384.

37. Ritterson LewC, TolanDR (2012) Targeting of several glycolytic enzymes using RNA interference reveals aldolase affects cancer cell proliferation through a non-glycolytic mechanism. J Biol Chem 287 : 42554–42563.

38. RangarajanES, ParkH, FortinE, SyguschJ, IzardT (2010) Mechanism of aldolase control of sorting nexin 9 function in endocytosis. J Biol Chem 285 : 11983–11990.

39. MerkulovaM, Hurtado-LorenzoA, HosokawaH, ZhuangZ, BrownD, et al. (2011) Aldolase directly interacts with ARNO and modulates cell morphology and acidic vesicle distribution. Am J Physiol Cell Physiol 300: C1442–1455.

40. WilflnigF, ThiamAR, OlarteMJ, WangJ, BeckR, et al. (2014) Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting. Elife 3: e01607.

41. ByunM, AbhyankarA, LelargeV, PlancoulaineS, PalanduzA, et al. (2010) Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma. J Exp Med 207 : 2307–2312.

42. DjouadiF, AubeyF, SchlemmerD, RuiterJP, WandersRJ, et al. (2005) Bezafibrate increases very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders. Hum Mol Genet 14 : 2695–2703.

43. MichotC, MamouneA, VamecqJ, ViouMT, HsiehLS, et al. (2013) Combination of lipid metabolism alterations and their sensitivity to inflammatory cytokines in human lipin-1-deficient myoblasts. Biochim Biophys Acta 1832 : 2103–2114.

44. GallucciS, ProvenzanoC, MazzarelliP, ScuderiF, BartoccioniE (1998) Myoblasts produce IL-6 in response to inflammatory stimuli. Int Immunol 10 : 267–273.

45. BeutlerE, BlumeKG, KaplanJC, LohrGW, RamotB, et al. (1977) International Committee for Standardization in Haematology: recommended methods for red-cell enzyme analysis. Br J Haematol 35 : 331–340.

46. LayzerRB, RowlandLP, RanneyHM (1967) Muscle phosphofructokinase deficiency. Arch Neurol 17 : 512–523.

47. RustinP, ChretienD, BourgeronT, GerardB, RotigA, et al. (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228 : 35–51.

48. DesseinAF, FontaineM, DobbelaereD, Mention-MulliezK, Martin-PonthieuA, et al. (2009) Deuterated palmitate-driven acylcarnitine formation by whole-blood samples for a rapid diagnostic exploration of mitochondrial fatty acid oxidation disorders. Clin Chim Acta 406 : 23–26.