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Abstract
Studies of the molecular mechanisms that are involved in stress responses (environmental or
physiological) have long been used to make links to disease states in humans. The nematode
model organism, Caenorhabditis elegans, undergoes a state of hypometabolism called the
‘dauer’ stage. This period of developmental arrest is characterized by a significant reduction
in metabolic rate, triggered by ambient temperature increase and restricted oxygen/ nutrients. C. elegans employs a number of signal transduction cascades in order to adapt to these
unfavourable conditions and survive for long times with severely reduced energy production.
The suppression of cellular metabolism, providing energetic homeostasis, is critical to the
survival of nematodes through the dauer period. This transition displays molecular mechanisms that are fundamental to control of hypometabolism across the animal kingdom. In
general, mammalian systems are highly inelastic to environmental stresses (such as extreme
temperatures and low oxygen), however, there is a great deal of conservation between the
signal transduction pathways of nematodes and mammals. Along with conserving many of the
protein targets in the stress response, many of the critical regulatory mechanisms are
maintained, and often differ only in their level of expression. Hence, the C. elegans model
outlines a framework of critical molecular mechanisms that may be employed in the future
as therapeutic targets for addressing disease states.
References
Yamashita O, and Hasegawa K. Embryonic diapause. In:
Kerkut G.A., Gilbert L.I., eds. Comprehensive Insect Physiology, Biochemistry and Pharmacology, vol. 1. Oxford: Pergamon
Press. 1985: 407–434.
2. Nakagaki M., Takei R., Nagashima E, and Yaginuma T. Cell
cycles in embryos of the silkworm, Bombyx mori: G2-arrest at
diapause stage. Roux’s Archives of Developmental Biology
1991; 200: 223–229.
3. MacRae T.H. Molecular chaperones, stress resistance and development in Artemia franciscana. Semin Cell Dev Biol. 2003;
14(5):251-258.
4. Renfree M.B, and Shaw G. Diapause. Annu Rev Physiol. 2000;
62: 353-375.
5. Lopes F.L., Desmarais J.A, and Murphy BD. Embryonic diapause and its regulation. Reproduction. 2004; 128(6): 669-678.
6. Storey K.B. Out cold: biochemical regulation of mammalian
hibernation. Gerontology. 2009; in press.
7. Hochachka P.W, and Lutz PL. Mechanism, Origin, and Evolution of Anoxia Tolerance in Animals. Comp Biochem Physiol B
2001; 130(4):435 – 459
8. Denlinger D.L. Regulation of Diapause. Annu Rev Entomol.
2002; 47:93 – 122.
9. Clegg J.S. Cryptobiosis – A Peculiar State of Biological Organization. Comp Biochem Physiol B. 2001; 128(4):613 – 24
10. Storey K.B. Life in the Slow Lane: Molecular Mechanisms of
Estivation. Comp Biochem Physiol A 2002; 133(3): 733 – 754
11. Storey K.B, and Storey JM. Metabolic Rate Depression and
Biochemical Adaptation in Anaerobiosis, Hibernation and Estivation. Quart Rev Biol. 1990; 65(2): 145 – 174
12. Storey K.B, and Storey JM. Metabolic Rate Depression in Animals: Transcriptional and Translational Control. Biol Rev Camb
Philos Soc. 2004; 79(1): 207 – 233
13. Heldmaier G., Ortmann S, and Elvert R. Natural Hypometabolism During Hibernation and Daily Torpor in Mammals. Respir
Physiol Neurobiol. 2004; 141(3): 317 – 329
14. Berk A.J. Regulation of Eukaryotic Transcription Factors by
Post-Translational Modification. Biochim Biophys Acta. 1989;
1009(2): 103 – 109
15. Johnson E.S. Protein Modification by SUMO. Annu Rev Biochem. 2004; 73: 355 – 382
16. Vanfleteren J.R, and Braeckman BP. Mechanisms of life span
determination in Caenorhabditis elegans. Neurobiol Aging.
1999; 20: 487 – 502
17. Burgering B.M.T, and Kops GJPL. Cell cycle and death control:
long live forkheads. Trends Biochem Sci. 2002; 27(7): 352-360
18. Beall M.J, and Pearce EJ. Transforming growth factor-beta and
insulin like signaling pathways in parasitic helminthes. Intl J
Parasit. 2002; 32: 399 – 404
19. Barbieri M., Bonafe M., Franceschi C, and Paolisso G. Insulin/IGF-I-Signaling Pathway: An Evolutionarily Conserved
Mechanism of Longevity from Yeast to Humans. Am J Physiol
2003; 285(5): E1064 – E1071
20. Ramnanan C.J., Groom A.G, and Storey KB. Akt and its Downstream Targets Play Key Roles in Mediating Dormancy in Land
Snails. Comp Biochem Physiol B. 2007; 148(2): 245 – 255
21. Osaki M., Oshimura M, and Ito H. PI3K-Akt Pathway: Its
Functions and Alterations in Human Cancer. Apoptosis. 2004;
9: 667 – 676
22. Jiang B.H, and Liu LZ. PI3K/PTEN signaling in Tumorigenesis
and Angiogenesis. Biochim Biophys Acta. 2008; 1784: 150 – 158
23. Tremblay M.L, and Giguere V. Phosphatases at the Heart of
FoxO Metabolic Control. Cell Metab. 2008; 7(2): 101 – 103
24. Lee R.Y.N., Hench J, and Ruvkun G. Regulation of C. elegans
DAF-16 and its human ortholog FKHRL1 by the Daf-2 insulin-like signaling pathway. Curr Biol 2001; 11: 1950-1957
25. Van der Horst A, and Burgering BM. Stressing the role of FoxO
Proteins in Lifespan and Disease. Nat Rev Mol Cell Biol. 2007;
8(6): 440 – 450
26. Obsilova V., Silhan J., Boura E., Teisinger J, and Obsil T. 14-3-3
Proteins: a Family of Versatile Molecular Regulators. Physiol
Res. 2008; 57(3): 11 – 21
27. Van Gorp A.C., Pomeranz K.M., Birkenkamp K.U., Hui R.C.,
Lam E.W, and Coffer PJ. Chronic Protein Kinase B (PKB/c-Akt)
Activation Leads to Apoptosis Induced by Oxidative
Stress-Mediated Foxo3a Transcriptional Up-Regulation. Cancer
Res. 2008; 66(22): 10760 – 10769
28. Proud C.G. Signaling to Translation: How Signal Transduction
Pathways Control the Protein Synthetic Machinery. Biochem J.
2007; 403(2): 217 – 234
29. Kotliarova S., Pastorino S., Kovell L.C., Kotliarov Y, Song H.,
Zhang W., Bailey R., Maric D., Zenklusen J.C., Lee J, and Fine
HA. Glycogen Synthase Kinase-3 Inhibition Induces Glioma
Cell Death Through c-MYC, Nuclear Factor-Kappa B, and
Glucose Regulation. Cancer Res. 2008; 68(16): 6643 – 6651
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