The protective effect of FGF21 on diabetes-induced male germ cell apoptosis is associated with up-regulated testicular AKT and AMPK/Sirt1/PGC-1α signaling

Endocrinology (United States)

Volumn 156, Issue 3, 2015, Pages 1156-1170

  Jiang, Xin ^a,c   Chen, Jun ^c,d   Zhang, Chi ^d   Zhang, Zhiguo ^a,c   Tan, Yi ^c,d   Feng, Wenke ^c   Skibba, Melissa ^c,d   Xin, Ying ^b,c   Cai, Lu ^c,d  

^a THE FIRST HOSPITAL OF JILIN UNIVERSITY   (China)

^b JILIN UNIVERSITY   (China)

^c University of Louisville School of Medicine   (United States)

^d WENZHOU MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

DNA NUCLEOTIDYLEXOTRANSFERASE; FIBROBLAST GROWTH FACTOR 21; GLYCOGEN SYNTHASE KINASE 3BETA; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PROTEIN KINASE B; PROTEIN MDM2; PROTEIN P53; SIRTUIN 1; TRIACYLGLYCEROL; FIBROBLAST GROWTH FACTOR; PPARGC1A PROTEIN, MOUSE; SIRT1 PROTEIN, MOUSE; TRANSCRIPTION FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; ENZYME PHOSPHORYLATION; FATTY ACID METABOLISM; FATTY ACID OXIDATION; GENE INACTIVATION; GERM CELL; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; IMMUNOFLUORESCENCE TEST; IMMUNOHISTOCHEMISTRY; LIPID PEROXIDATION; MOUSE; NICK END LABELING; NITROSATIVE STRESS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; SPERMATOCYTE; SPERMATOGENESIS; SPERMATOGONIUM; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; TESTIS; TESTIS WEIGHT; TRIACYLGLYCEROL BLOOD LEVEL; WESTERN BLOTTING; ANIMAL; CYTOLOGY; EXPERIMENTAL DIABETES MELLITUS; GENE EXPRESSION REGULATION; GENETICS; KNOCKOUT MOUSE; MALE; METABOLISM; PHYSIOLOGY;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; APOPTOSIS; DIABETES MELLITUS, EXPERIMENTAL; FIBROBLAST GROWTH FACTORS; GENE EXPRESSION REGULATION; GERM CELLS; MALE; MICE; MICE, KNOCKOUT; PROTO-ONCOGENE PROTEINS C-AKT; SIRTUIN 1; TESTIS; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84923884674     PISSN: 00137227     EISSN: 19457170     Source Type: Journal    
DOI: 10.1210/en.2014-1619     Document Type: Article

References (50)

1. Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARα and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007;5:426-437.
2. Gälman C, Lundåsen T, Kharitonenkov A, et al. The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARα activation in man. Cell Metab. 2008;8:169-174.
3. Hondares E, Iglesias R, Giralt A, et al. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem. 2011;286:12983-12990.
4. Fon Tacer K, Bookout AL, Ding X, et al. Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol. 2010;24:2050-2064.
5. Planavila A, Redondo I, Hondares E, et al. Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat Commun. 2013;4:2019.
6. Cuevas-Ramos D, Aguilar-Salinas CA, Gómez-Pérez FJ. Metabolic actions of fibroblast growth factor 21. Curr Opin Pediatr. 2012;24:523-529.
7. Jiang X, Zhang C, Xin Y, et al. Protective effect of FGF21 on type 1 diabetes-induced testicular apoptotic cell death probably via both mitochondrial- and endoplasmic reticulum stress-dependent pathways in the mouse model. Toxicol Lett. 2013;219:65-76.
8. Zhao Y, Tan Y, Dai J, et al. Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett. 2011;200:100-106.
9. Cai L, Klein JB, Kang YJ. Metallothionein inhibits peroxynitriteinduced DNA and lipoprotein damage. J Biol Chem. 2000;275:38957-38960.
10. Dummler B, Tschopp O, Hynx D, Yang ZZ, Dirnhofer S, Hemmings BA. Life with a single isoform of Akt: mice lacking Akt2 and Akt3 are viable but display impaired glucose homeostasis and growth deficiencies. Mol Cell Biol. 2006;26:8042-8051.
11. Guo TB, Chan KC, Hakovirta H, et al. Evidence for a role of glycogen synthase kinase-3 β in rodent spermatogenesis. J Androl. 2003;24:332-342.
12. Zhao Y, Tan Y, Dai J, et al. Zinc deficiency exacerbates diabetic down-regulation of Akt expression and function in the testis: essential roles of PTEN, PTP1B and TRB3. J Nutr Biochem. 2012;23:1018-1026.
13. Wang Y, Feng W, Xue W, et al. Inactivation of GSK-3β by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Diabetes. 2009;58:1391-1402.
14. Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol. 2007;8:774-785.
15. Shaw RJ, Kosmatka M, Bardeesy N, et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA. 2004;101:3329-3335.
16. Galardo MN, Riera MF, Pellizzari EH, Cigorraga SB, Meroni SB. The AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-b-D-ribonucleoside, regulates lactate production in rat Sertoli cells. J Mol Endocrinol. 2007;39:279-288.
17. Riera MF, Galardo MN, Pellizzari EH, Meroni SB, Cigorraga SB. Molecular mechanisms involved in Sertoli cell adaptation to glucose deprivation. Am J Physiol Endocrinol Metab. 2009;297:E907-E914.
18. Coussens M, Maresh JG, Yanagimachi R, Maeda G, Allsopp R. Sirt1 deficiency attenuates spermatogenesis and germ cell function. PLoS One. 2008;3:e1571.
19. ReznickRM,Shulman GI. The role of AMP-activated protein kinase in mitochondrial biogenesis. J Physiol. 2006;574:33-39.
20. Alves MG, Martins AD, Rato L, Moreira PI, Socorro S, Oliveira PF. Molecular mechanisms beyond glucose transport in diabetes-related male infertility. Biochim Biophys Acta. 2013;1832:626-635.
21. Holland WL, Adams AC, Brozinick JT, et al. An FGF21-adiponec-tin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab. 2013;17:790-797.
22. Chau MD, Gao J, Yang Q, Wu Z, Gromada J. Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1α pathway. Proc Natl Acad Sci USA. 2010;107:12553-12558.
23. Cong WT, Ling J, Tian HS, et al. Proteomic study on the protective mechanism of fibroblast growth factor 21 to ischemia-reperfusion injury. Can J Physiol Pharmacol. 2013;91:973-984.
24. Rasoulpour T, DiPalma K, Kolvek B, Hixon M. Akt1 suppresses radiation-induced germ cell apoptosis in vivo. Endocrinology. 2006;147:4213-4221.
25. Santos-Ahmed J, Brown C, Smith SD, et al. Akt1 protects against germ cell apoptosis in the postnatal mouse testis following lactational exposure to 6-N-propylthiouracil. Reprod Toxicol. 2011;31:17-25.
26. Chen WS, Xu PZ, Gottlob K, et al. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev. 2001;15:2203-2208.
27. Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;9:59-71.
28. Fuchs SY, Adler V, Buschmann T, Wu X, Ronai Z. Mdm2 association with p53 targets its ubiquitination. Oncogene. 1998;17:2543-2547.
29. Pitetti JL, Calvel P, Zimmermann C, et al. An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice. Mol Endocrinol. 2013;27:814-827.
30. Spaliviero JA, Jimenez M, Allan CM, Handelsman DJ. Luteinizing hormone receptor-mediated effects on initiation of spermatogenesis in gonadotropin-deficient (hpg) mice are replicated by testosterone. Biol Reprod. 2004;70:32-38.
31. Wang H, Xiao Y, Fu L, et al. High-level expression and purification of soluble recombinant FGF21 protein by SUMO fusion in Escherichia coli. BMC Biotechnol. 2010;10:14.
32. Kim ST, Omurtag K, Moley KH. Decreased spermatogenesis, fertility, and altered Slc2A expression in Akt1-/- and Akt2-/- testes and sperm. Reprod Sci. 2012;19:31-42.
33. Mudò G, Mäkelä J, Di Liberto V, et al. Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson's disease. Cell Mol Life Sci. 2012;69:1153-1165.
34. Sapkota GP, Kieloch A, Lizcano JM, et al. Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/ STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth. J Biol Chem. 2001;276:19469-19482.
35. Li GY, Xie P, Li HY, Hao L, Xiong Q, Qiu T. Involment of p53, Bax, and Bcl-2 pathway in microcystins-induced apoptosis in rat testis. Environ Toxicol. 2011;26:111-117.
36. Rato L, Duarte AI, Tomás GD, et al. Pre-diabetes alters testicular PGC1-α/SIRT3 axis modulating mitochondrial bioenergetics and oxidative stress. Biochim Biophys Acta. 2014;1837:335-344.
37. Yu X, Zhang L, Yang X, et al. Salvianolic acid A protects the peripheral nerve function in diabetic rats through regulation of the AMPK-PGC1α-Sirt3 axis. Molecules. 2012;17:11216-11228.
38. Esteve-Puig R, Canals F, Colome N, Merlino G, Recio JA. Uncoupling of theLKB1-AMPKα energy sensor pathway by growth factors and oncogenic BRAF. PLoS One. 2009;4:e4771.
39. Wente W, Efanov AM, Brenner M, et al. Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes. 2006;55:2470-2478.
40. Kim HW, Lee JE, Cha JJ, et al. Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice. Endocrinology. 2013;154:3366-3376.
41. Hay N. Akt isoforms and glucose homeostasis - the leptin connection. Trends Endocrinol Metab. 2011;22:66-73.
42. Yin Y, Stahl BC, DeWolf WC, Morgentaler A. p53-mediated germ cell quality control in spermatogenesis. Dev Biol. 1998;204:165-171.
43. Ogawara Y, Kishishita S, Obata T, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J BiolChem. 2002;277:21843-21850.
44. De Miguel MP, Donovan PJ. Determinants of retroviral-mediated gene delivery to mouse spermatogonia. Biol Reprod. 2003;68:860-866.
45. Limesand KH, Schwertfeger KL, Anderson SM. MDM2 is required for suppression of apoptosis by activated Akt1 in salivary acinar cells. Mol Cell Biol. 2006;26:8840-8856.
46. Zhang L, Sun S, Zhou J, et al. Knockdown of Akt1 promotes Akt2 upregulation and resistance to oxidative-stress-induced apoptosis through control of multiple signaling pathways. Antioxid Redox Signal. 2011;15:1-17.
47. Samuel SM, Thirunavukkarasu M, Penumathsa SV, Paul D, Maulik N. Akt/FOXO3a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress in rat in vivo model of myocardial infarction: switching gears toward survival and longevity. J Agric Food Chem. 2008;56:9692-9698.
48. Zhao H, Xu S, Wang Z, et al. Repetitive exposures to low-dose x-rays attenuate testicular apoptotic cell death in streptozotocininduced diabetes rats. Toxicol Lett. 2010;192:356-364.
49. Cai L, Li W, Wang G, Guo L, Jiang Y, Kang YJ. Hyperglycemiainduced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway. Diabetes. 2002;51:1938-1948.
50. Gaich G, Chien JY, Fu H, et al. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab. 2013;18:333-340.