Hostname: page-component-76fb5796d-2lccl Total loading time: 0 Render date: 2024-04-25T16:15:05.341Z Has data issue: false hasContentIssue false
  • English
  • Français

Growth restriction before and after birth increases kinase signaling pathways in the adult rat heart

Published online by Cambridge University Press:  19 November 2010

G. D. Wadley ,
M. E. Wlodek ,
G. Ng ,
C. Goodman ,
C. Stathis  and
G. K. McConell
G. D. Wadley
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
M. E. Wlodek
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
G. Ng
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
C. Goodman
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
C. Stathis
Affiliation:
Institute of Sport, Exercise and Active Living and the School of Biomedical and Health Sciences, Victoria University, Victoria, Australia
G. K. McConell*
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia Institute of Sport, Exercise and Active Living and the School of Biomedical and Health Sciences, Victoria University, Victoria, Australia
*
*Address for correspondence: Dr G. McConell, Institute of Sport, Exercise and Active Living and the School of Biomedical and Health Sciences, Victoria University, Victoria 8001, Australia. (Email glenn.mcconell@vu.edu.au)
Get access Rights & Permissions [Opens in a new window]

Abstract

To investigate the mechanisms for the previously reported development of adult cardiac hypertrophy in male rats following growth restriction, the levels of oxidative stress and activation of signaling kinases were measured in the left ventricle (LV) of adult rat offspring. In experiment one, bilateral uterine vessel ligation to induce uteroplacental insufficiency and growth restriction in the offspring (Restricted) or sham surgery was performed during pregnancy. Litters from sham mothers had litter size either reduced (Reduced Litter), which also restricted postnatal growth, or were left unaltered (Control). In males, Reduced Litter offspring had increased LV phosphorylation of AMPKα, p38 MAPK and Akt compared with Restricted and Controls (P < 0.05). In females, both Restricted and Reduced Litter adult offspring had increased LV phosphorylation of p38 MAPK and Akt, however, only Restricted offspring had increased phosphorylation of AMPKα (P < 0.05). In addition, only Restricted male offspring displayed LV oxidative stress (P < 0.05). Experiment two investigated in mothers exposed to uteroplacental insufficiency or sham surgery the effects of cross-fostering offspring at birth, and therefore the effects of the postnatal lactational environment. Surprisingly, the cross-fostering itself resulted in increased LV phosphorylation of AMPKα and Akt in females and increased phosphorylation of Akt in males compared with Control non-cross-fostered offspring (P < 0.05). In conclusion, kinase signaling in the adult LV can be programmed by uteroplacental insufficiency induced growth restriction in a gender-specific manner. In addition, the heart of adult rats is also sensitive to programming following the postnatal intervention of cross-fostering alone as well as by postnatal growth restriction.

Keywords

developmentcardiac musclekinasesfoetal programming
Type
Original Articles
Information
Journal of Developmental Origins of Health and Disease , Volume 1 , Issue 6 , December 2010 , pp. 376 - 385
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Barker, DJ, Osmond, C, Golding, J, Kuh, D, Wadsworth, ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298, 564–567.CrossRefGoogle ScholarPubMed
2. Eriksson, J, Forsen, T, Tuomilehto, J, Osmond, C, Barker, D. Fetal and childhood growth and hypertension in adult life. Hypertension. 2000; 36, 790–794.CrossRefGoogle ScholarPubMed
3. Storgaard, H, Poulsen, P, Ling, C, Groop, L, Vaag, AA. Genetic and nongenetic determinants of skeletal muscle glucose transporter 4 messenger ribonucleic acid levels and insulin action in twins. J Clin Endocrinol Metab. 2006; 91, 702–708.CrossRefGoogle ScholarPubMed
4. Eriksson, JG, Forsen, T, Tuomilehto, J, Osmond, C, Barker, DJ. Early growth and coronary heart disease in later life: longitudinal study. BMJ. 2001; 322, 949–953.Google Scholar
5. Forsen, TJ, Eriksson, JG, Osmond, C, Barker, DJ. The infant growth of boys who later develop coronary heart disease. Ann Med. 2004; 36, 389–392.Google Scholar
6. Wlodek, ME, Mibus, A, Tan, A, et al. Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol. 2007; 18, 1688–1696.CrossRefGoogle ScholarPubMed
7. Vickers, MH, Breier, BH, Cutfield, WS, Hofman, PL, Gluckman, PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000; 279, E83–E87.CrossRefGoogle ScholarPubMed
8. Wlodek, ME, Westcott, K, Siebel, AL, Owens, JA, Moritz, KM. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats. Kidney Int. 2008; 74, 187–195.CrossRefGoogle ScholarPubMed
9. Tsirka, AE, Gruetzmacher, EM, Kelley, DE, et al. Myocardial gene expression of glucose transporter 1 and glucose transporter 4 in response to uteroplacental insufficiency in the rat. J Endocrinol. 2001; 169, 373–380.CrossRefGoogle ScholarPubMed
10. Siebel, AL, Mibus, A, De Blasio, MJ, et al. Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring. Endocrinology. 2008; 149, 3067–3076.CrossRefGoogle ScholarPubMed
11. Wadley, GD, Siebel, AL, Cooney, GJ, et al. Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat. Am J Physiol Endocrinol Metab. 2008; 294, E861–E869.CrossRefGoogle Scholar
12. Dyck, JRB, Lopaschuk, GD. AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol. 2006; 574, 95–112.CrossRefGoogle ScholarPubMed
13. Pelletier, A, Joly, E, Prentki, M, Coderre, L. Adenosine 5’-monophosphate-activated protein kinase and p38 mitogen-activated protein kinase participate in the stimulation of glucose uptake by dinitrophenol in adult cardiomyocytes. Endocrinology. 2005; 146, 2285–2294.CrossRefGoogle Scholar
14. Shiojima, I, Walsh, K. Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev. 2006; 20, 3347–3365.CrossRefGoogle ScholarPubMed
15. Clerk, A, Sugden, PH. Inflame my heart (by p38-MAPK). Circ Res. 2006; 99, 455–458.CrossRefGoogle ScholarPubMed
16. Liang, Q, Molkentin, JD. Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models. J Mol Cell Cardiol. 2003; 35, 1385–1394.Google Scholar
17. Baines, CP, Molkentin, JD. STRESS signaling pathways that modulate cardiac myocyte apoptosis. J Mol Cell Cardiol. 2005; 38, 47–62.Google Scholar
18. Wang, Y. Mitogen-activated protein kinases in heart development and diseases. Circulation. 2007; 116, 1413–1423.Google Scholar
19. Li, J, Miller, EJ, Ninomiya-Tsuji, J, IIIRussell, RR, Young, LH. AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res. 2005; 97, 872–879.CrossRefGoogle ScholarPubMed
20. Young, LH, Li, J, Baron, SJ, Russell, RR. AMP-activated protein kinase: a key stress signaling pathway in the heart. Trends Cardiovasc Med. 2005; 15, 110–118.CrossRefGoogle ScholarPubMed
21. Gavete, ML, Agote, M, Martin, MA, Alvarez, C, Escriva, F. Effects of chronic undernutrition on glucose uptake and glucose transporter proteins in rat heart. Endocrinology. 2002; 143, 4295–4303.CrossRefGoogle ScholarPubMed
22. Langdown, ML, Holness, MJ, Sugden, MC. Early growth retardation induced by excessive exposure to glucocorticoids in utero selectively increases cardiac GLUT1 protein expression and Akt/protein kinase B activity in adulthood. J Endocrinol. 2001; 169, 11–22.Google Scholar
23. Takimoto, E, Kass, DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension. 2007; 49, 241–248.Google Scholar
24. Seddon, M, Looi, YH, Shah, AM. Oxidative stress and redox signalling in cardiac hypertrophy and heart failure. Heart. 2007; 93, 903–907.CrossRefGoogle ScholarPubMed
25. Battista, MC, Calvo, E, Chorvatova, A, et al. Intra-uterine growth restriction and the programming of left ventricular remodelling in female rats. J Physiol. 2005; 565, 197–205.Google Scholar
26. Horie, T, Ono, K, Nagao, K, et al. Oxidative stress induces GLUT4 translocation by activation of PI3-K/Akt and dual AMPK kinase in cardiac myocytes. J Cell Physiol. 2008; 215, 733–742.Google Scholar
27. Dolinsky, VW, Dyck, JR. Role of AMP-activated protein kinase in healthy and diseased hearts. Am J Physiol Heart Circ Physiol. 2006; 291, H2557–H2569.CrossRefGoogle ScholarPubMed
28. O’Dowd, R, Kent, JC, Moseley, JM, Wlodek, ME. Effects of uteroplacental insufficiency and reducing litter size on maternal mammary function and postnatal offspring growth. Am J Physiol Regul Integr Comp Physiol. 2008; 294, R539–R548.CrossRefGoogle ScholarPubMed
29. Siebel, AL, Gallo, LA, Guan, TC, Owens, JA, Wlodek, ME. Cross-fostering and improved lactation ameliorates deficits in endocrine pancreatic morphology in growth-restricted adult male rat offspring. Journal of Developmental Origins of Health and Disease. 2010; 1, 234–244.CrossRefGoogle ScholarPubMed
30. Wlodek, ME, Westcott, KT, O’Dowd, R, et al. Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R1620–R1627.CrossRefGoogle ScholarPubMed
31. Moritz, KM, Mazzuca, MQ, Siebel, AL, et al. Uteroplacental insufficiency causes a nephron deficit, modest renal insufficiency but no hypertension with ageing in female rats. J Physiol. 2009; 587, 2635–2646.CrossRefGoogle ScholarPubMed
32. Beauloye, C, Marsin, A-S, Bertrand, L, et al. Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides. FEBS letters. 2001; 505, 348–352.CrossRefGoogle ScholarPubMed
33. Altarejos, JY, Taniguchi, M, Clanachan, AS, Lopaschuk, GD. Myocardial ischemia differentially regulates LKB1 and an alternate 5’-AMP-activated protein kinase kinase. J Biol Chem. 2005; 280, 183–190.CrossRefGoogle Scholar
34. Wadley, GD, Lee-Young, RS, Canny, BJ, et al. Effect of exercise intensity and hypoxia on skeletal muscle AMPK signaling and substrate metabolism in humans. Am J Physiol Endocrinol Metab. 2006; 290, E694–E702.CrossRefGoogle ScholarPubMed
35. Tian, R, Musi, N, D’Agostino, J, Hirshman, MF, Goodyear, LJ. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation. 2001; 104, 1664–1669.Google Scholar
36. Xing, Y, Musi, N, Fujii, N, et al. Glucose metabolism and energy homeostasis in mouse hearts overexpressing dominant negative alpha2 subunit of AMP-activated protein kinase. J Biol Chem. 2003; 278, 28372–28377.Google Scholar
37. Botker, HE, Helligso, P, Kimose, HH, Thomassen, AR, Nielsen, TT. Determination of high energy phosphates and glycogen in cardiac and skeletal muscle biopsies, with special reference to influence of biopsy technique and delayed freezing. Cardiovasc Res. 1994; 28, 524–527.Google Scholar
38. Sandstrom, ME, Zhang, SJ, Bruton, J, et al. Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle. J Physiol. 2006; 575, 251–262.CrossRefGoogle ScholarPubMed
39. Sandstrom, ME, Zhang, S-J, Westerblad, H, Katz, A. Mechanical load plays little role in contraction-mediated glucose transport in mouse skeletal muscle. J Physiol. 2007; 579, 527–534.CrossRefGoogle ScholarPubMed
40. Alvarez, MC, Caldiz, C, Fantinelli, JC, et al. Is cardiac hypertrophy in spontaneously hypertensive rats the cause or the consequence of oxidative stress. Hypertens Res. 2008; 31, 1465–1476.CrossRefGoogle ScholarPubMed
41. Vuguin, P, Raab, E, Liu, B, Barzilai, N, Simmons, R. Hepatic insulin resistance precedes the development of diabetes in a model of intrauterine growth retardation. Diabetes. 2004; 53, 2617–2622.CrossRefGoogle Scholar
42. Simmons, RA, Suponitsky-Kroyter, I, Selak, MA. Progressive accumulation of mitochondrial DNA mutations and decline in mitochondrial function lead to beta-cell failure. J Biol Chem. 2005; 280, 28785–28791.CrossRefGoogle ScholarPubMed
43. Selak, MA, Storey, BT, Peterside, I, Simmons, RA. Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth-retarded rats. Am J Physiol Endocrinol Metab. 2003; 285, E130–E137.CrossRefGoogle ScholarPubMed
44. Thamotharan, M, Shin, BC, Suddirikku, DT, et al. GLUT4 expression and subcellular localization in the intrauterine growth-restricted adult rat female offspring. Am J Physiol Endocrinol Metab. 2005; 288, E935–E947.Google Scholar
45. Camper-Kirby, D, Welch, S, Walker, A, et al. Myocardial Akt activation and gender: increased nuclear activity in females versus males. Circ Res. 2001; 88, 1020–1027.CrossRefGoogle ScholarPubMed
46. Ojeda, NB, Grigore, D, Robertson, EB, Alexander, BT. Estrogen protects against increased blood pressure in postpubertal female growth restricted offspring. Hypertension. 2007; 50, 679–685.CrossRefGoogle ScholarPubMed
47. Simmons, RA, Templeton, LJ, Gertz, SJ. Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes. 2001; 50, 2279–2286.CrossRefGoogle Scholar
48. Liu, D, Diorio, J, Tannenbaum, B, et al. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science. 1997; 277, 1659–1662.Google Scholar
49. Diorio, J, Meaney, MJ. Maternal programming of defensive responses through sustained effects on gene expression. J Psychiatry Neurosci. 2007; 32, 275–284.Google ScholarPubMed