Rheostasis (biology): Difference between revisions
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* Lymphocyte persistence and expansion appear to be regulated by survival and programmed cell death ([[apoptosis]]) rheostatically in dividing cells by the interaction of two protein families, restraining lymphocyte expansion under adverse conditions.<ref>Alves,N.L.; Derks,I.A.; Berk,E.; Spijker,R.; van Lier,R.A.; Eldering,E.. (2006) [http://dx.doi.org/10.1016/j.immuni.2006.03.018 The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells.] ''Immunity''24(6):703-716. PMID 16782027. | * Lymphocyte persistence and expansion appear to be regulated by survival and programmed cell death ([[apoptosis]]) rheostatically in dividing cells by the interaction of two protein families, restraining lymphocyte expansion under adverse conditions.<ref>Alves,N.L.; Derks,I.A.; Berk,E.; Spijker,R.; van Lier,R.A.; Eldering,E.. (2006) [http://dx.doi.org/10.1016/j.immuni.2006.03.018 The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells.] ''Immunity''24(6):703-716. PMID 16782027. | ||
* Throughout lymphocyte development, cellular persistence and expansion are tightly regulated by survival and apoptosis. Within the Bcl-2 family, distinct apoptogenic BH3-only members like Bid, Bim, and Puma appear to function in specific cell death pathways. We found that naive human T cells after mitogenic activation, apart from expected protective Bcl-2 members, also rapidly upregulate the BH3-only protein Noxa in a p53-independent fashion. The specific role of Noxa became apparent during glucose limitation and involves interaction with the labile Bcl-2 homolog Mcl-1. Knockdown of Noxa or Mcl-1 results in protection or susceptibility, respectively, to apoptosis induced by glucose deprivation. Declining Mcl-1 levels and apoptosis induction are inversely correlated to Noxa levels and prevented by readdition of glucose. We propose that the Noxa/Mcl-1 axis is an apoptosis rheostat in dividing cells, in a selective pathway that functions to restrain lymphocyte expansion and can be triggered by glucose deprivation.</ref> | * Throughout lymphocyte development, cellular persistence and expansion are tightly regulated by survival and apoptosis. Within the Bcl-2 family, distinct apoptogenic BH3-only members like Bid, Bim, and Puma appear to function in specific cell death pathways. We found that naive human T cells after mitogenic activation, apart from expected protective Bcl-2 members, also rapidly upregulate the BH3-only protein Noxa in a p53-independent fashion. The specific role of Noxa became apparent during glucose limitation and involves interaction with the labile Bcl-2 homolog Mcl-1. Knockdown of Noxa or Mcl-1 results in protection or susceptibility, respectively, to apoptosis induced by glucose deprivation. Declining Mcl-1 levels and apoptosis induction are inversely correlated to Noxa levels and prevented by readdition of glucose. We propose that the Noxa/Mcl-1 axis is an apoptosis rheostat in dividing cells, in a selective pathway that functions to restrain lymphocyte expansion and can be triggered by glucose deprivation.</ref> | ||
* The education of developing natural killer (NK) cells for optimal functional responsiveness at maturity — specialized to kill certain types of injurious target cells — appears to operate rheostatically, individual NK cells quantitatively tuned by graded inhibitory inputs during development.<ref>Brodin,P.; Karre,K.; Hoglund,P. (2009) [http://dx.doi.org/10.1016/j.it.2009.01.006 NK cell education: not an on-off switch but a tunable rheostat.] ''Trends Immuol.'' 30(4):143-149. PMID 19282243. * Heterogeneity in the natural killer (NK) cell population is determined by variegated expression of polygenic and polymorphic receptors and distinct phenotypes and functions of NK cell subsets. Here, we outline an additional heterogeneity at the level of MHC-dependent education of NK cells. Based on data obtained using polychromatic flow cytometry and mice with single MHC class I alleles, we argue that NK cell responsiveness is tuned along a continuum determined by the strength of the inhibitory input received by the individual NK cell during education. This model has implications for the use of NK cells in therapeutic settings and affects interpretations of how NK cells control virus infections and regulate autoimmunity.</ref> | |||
==References== | ==References== | ||
<references/> | <references/> | ||
Revision as of 14:47, 29 July 2009
Rheostasis refers to biochemical and physiological processes that, through graduated quantitative regulation, serve the adaptive needs of an organism facing internal or external environmental challenges. Physiological rheostasis operates much like an electrician’s rheostat graduates current. As discussed in the article on allostasis, the human living system persists in the living state not only through mechanisms that regulate constancy of critical biological variables and processes — homeostasis — but also through mechanisms that change the set-point ranges of biological variables and processes so as to adapt to changing, sometimes seriously threatening circumstances.
Biologists use the term 'on/off switch' when such set-point-range re-setting occurs in a binary ('on/off') type manner, and 'rheostat' when the regulatory mechanism operates in a graduated, or quantitative, manner. Biologists see one example of rheostasis in the phenomenon of quantitative gene expression regulation, when it occurs by continuously variable 'switches' quantitatively coupled to enzyme activity.[1] [2]
Rheostasis elucidates many facets of mammalian physiology in relation to homeostasis, allostasis, and systems biology.[3]
- Lymphocyte persistence and expansion appear to be regulated by survival and programmed cell death (apoptosis) rheostatically in dividing cells by the interaction of two protein families, restraining lymphocyte expansion under adverse conditions.[4]
- The education of developing natural killer (NK) cells for optimal functional responsiveness at maturity — specialized to kill certain types of injurious target cells — appears to operate rheostatically, individual NK cells quantitatively tuned by graded inhibitory inputs during development.[5]
References
- ↑ Hazzalin CA, Mahadevan LC. (2002) MAPK-regulated transcription: a continuously variable gene switch? Nat Rev Mol Cell Biol 3:30-40.
- ↑ Bardwell L. (2008) Signal transduction: turning a switch into a rheostat. Curr Biol 18:R910-R912.
- ↑ Mrosovsky N. (1990) Rheostasis: the physiology of change. Oxford University Press. ISBN 0-19-506184-5.
- ↑ Alves,N.L.; Derks,I.A.; Berk,E.; Spijker,R.; van Lier,R.A.; Eldering,E.. (2006) The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells. Immunity24(6):703-716. PMID 16782027.
- Throughout lymphocyte development, cellular persistence and expansion are tightly regulated by survival and apoptosis. Within the Bcl-2 family, distinct apoptogenic BH3-only members like Bid, Bim, and Puma appear to function in specific cell death pathways. We found that naive human T cells after mitogenic activation, apart from expected protective Bcl-2 members, also rapidly upregulate the BH3-only protein Noxa in a p53-independent fashion. The specific role of Noxa became apparent during glucose limitation and involves interaction with the labile Bcl-2 homolog Mcl-1. Knockdown of Noxa or Mcl-1 results in protection or susceptibility, respectively, to apoptosis induced by glucose deprivation. Declining Mcl-1 levels and apoptosis induction are inversely correlated to Noxa levels and prevented by readdition of glucose. We propose that the Noxa/Mcl-1 axis is an apoptosis rheostat in dividing cells, in a selective pathway that functions to restrain lymphocyte expansion and can be triggered by glucose deprivation.
- ↑ Brodin,P.; Karre,K.; Hoglund,P. (2009) NK cell education: not an on-off switch but a tunable rheostat. Trends Immuol. 30(4):143-149. PMID 19282243. * Heterogeneity in the natural killer (NK) cell population is determined by variegated expression of polygenic and polymorphic receptors and distinct phenotypes and functions of NK cell subsets. Here, we outline an additional heterogeneity at the level of MHC-dependent education of NK cells. Based on data obtained using polychromatic flow cytometry and mice with single MHC class I alleles, we argue that NK cell responsiveness is tuned along a continuum determined by the strength of the inhibitory input received by the individual NK cell during education. This model has implications for the use of NK cells in therapeutic settings and affects interpretations of how NK cells control virus infections and regulate autoimmunity.