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Adaptive response, evidence of cross-resistance and its potential clinical use.

Milisav I, Poljsak B, Suput D - Int J Mol Sci (2012)

Bottom Line: Stress responses are mechanisms used by organisms to adapt to and overcome stress stimuli.Studies have reported life-prolonging effects of a wide variety of so-called stressors, such as oxidants, heat shock, some phytochemicals, ischemia, exercise and dietary energy restriction, hypergravity, etc.These stress responses, which result in enhanced defense and repair and even cross-resistance against multiple stressors, may have clinical use and will be discussed, while the emphasis will be on the effects/cross-effects of oxidants.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, Ljubljana SI-1000, Slovenia; E-Mail: dusan.suput@mf.uni-lj.si ; Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, Ljubljana SI-1000, Slovenia; E-Mail: borut.poljsak@zf.uni-lj.si.

ABSTRACT
Organisms and their cells are constantly exposed to environmental fluctuations. Among them are stressors, which can induce macromolecular damage that exceeds a set threshold, independent of the underlying cause. Stress responses are mechanisms used by organisms to adapt to and overcome stress stimuli. Different stressors or different intensities of stress trigger different cellular responses, namely induce cell repair mechanisms, induce cell responses that result in temporary adaptation to some stressors, induce autophagy or trigger cell death. Studies have reported life-prolonging effects of a wide variety of so-called stressors, such as oxidants, heat shock, some phytochemicals, ischemia, exercise and dietary energy restriction, hypergravity, etc. These stress responses, which result in enhanced defense and repair and even cross-resistance against multiple stressors, may have clinical use and will be discussed, while the emphasis will be on the effects/cross-effects of oxidants.

No MeSH data available.


Related in: MedlinePlus

Simplified core stress signaling pathways. The kinase mTOR is a part of complexes mTORC1 and mTORC2. mTORC1 is at the bottom of the PI3-kinase (PI3K) and protein kinase B (AKT) signaling pathways, which receive signals from growth factor receptors at the plasma membrane [55]. mTORC1 also receives signals from p53 through AMPK in the case of DNA damage, through AMPK in the case of energy deficit, through IκB kinase β (IKKβ) during inflammation, etc. [104]. mTORC1 is inhibited by the heterodimer of tuberous sclerosis proteins TSC1 and TSC2 (TSC1/2). Sustained activation of mTORC1 blocks growth factor signaling through activation of the negative loop that inhibits PI3K signaling [101]. The activation of mTORC1 promotes protein synthesis mainly by phosphorylating the kinase S6K and through the regulator of translation 4E-BP1 [102,104]. The biogenesis of lipids is induced through the activation of transcription factors SREBP1 and PPARγ [103]. The energy metabolism is activated through the activation of expression of hypoxia inducing factor 1α (HIF1α) [104]. The active complex mTORC1 promotes anabolism and inhibits catabolism by blocking autophagy through phosphorylation of a complex that consists of ULK1-Atg13-FIP200 and inhibits lysosome biogenesis likely through the transcription factor EB (TFEB) [104]. mTORC2 (not shown) is activated by growth factors and regulates the organization of actin cytoskeleton through protein kinase C-α (PKC-α); it also regulates the serum- and glucocorticoid-induced kinase 1 (SGK1) that controls ion transport and growth; and AKT, which regulates metabolism, survival, apoptosis, growth and proliferation through phosphorylation of several effectors, including TSC1/2 [104].
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f5-ijms-13-10771: Simplified core stress signaling pathways. The kinase mTOR is a part of complexes mTORC1 and mTORC2. mTORC1 is at the bottom of the PI3-kinase (PI3K) and protein kinase B (AKT) signaling pathways, which receive signals from growth factor receptors at the plasma membrane [55]. mTORC1 also receives signals from p53 through AMPK in the case of DNA damage, through AMPK in the case of energy deficit, through IκB kinase β (IKKβ) during inflammation, etc. [104]. mTORC1 is inhibited by the heterodimer of tuberous sclerosis proteins TSC1 and TSC2 (TSC1/2). Sustained activation of mTORC1 blocks growth factor signaling through activation of the negative loop that inhibits PI3K signaling [101]. The activation of mTORC1 promotes protein synthesis mainly by phosphorylating the kinase S6K and through the regulator of translation 4E-BP1 [102,104]. The biogenesis of lipids is induced through the activation of transcription factors SREBP1 and PPARγ [103]. The energy metabolism is activated through the activation of expression of hypoxia inducing factor 1α (HIF1α) [104]. The active complex mTORC1 promotes anabolism and inhibits catabolism by blocking autophagy through phosphorylation of a complex that consists of ULK1-Atg13-FIP200 and inhibits lysosome biogenesis likely through the transcription factor EB (TFEB) [104]. mTORC2 (not shown) is activated by growth factors and regulates the organization of actin cytoskeleton through protein kinase C-α (PKC-α); it also regulates the serum- and glucocorticoid-induced kinase 1 (SGK1) that controls ion transport and growth; and AKT, which regulates metabolism, survival, apoptosis, growth and proliferation through phosphorylation of several effectors, including TSC1/2 [104].

Mentions: As the consequences of stress are alterations in cellular metabolism, growth and division, it is no surprise that the main signaling pathways that regulate cell growth, metabolism, senescence and apoptosis also regulate the stress responses. The complex mTORC1 with its catalytic subunit mTOR regulates growth by maintaining the balance between the anabolic processes, like macromolecular synthesis, and catabolic processes, such as autophagy (Figure 5). mTORC1 mediates cellular responses to many types of stress, like DNA damage and drops in the level of energy, oxygen, amino acids and glucose. mTORC1 is at the bottom of PI3K and AKT signaling pathways, which receive signals from growth factor receptors at the plasma membrane and other inputs [55]. mTORC1 consists of mTOR and regulatory-associated protein of mTOR (raptor), mammalian lethal with Sec13 protein 8 (mLST8), proline-rich AKT substrate 40 kDa (PRAS40), and DEP-domain-containing mTOR-interacting protein (Deptor). The small G protein Rheb in the GTP-bound form stimulates the activity of mTORC1. Rheb is inhibited by the heterodimer of tuberous sclerosis proteins TSC1 and TSC2 (TSC1/2), which convert Rheb into an inactive GDP-bound state. Growth factors promote activities of several kinases, such as AKT, Erk and Rsk, which phosphorylate TSC1/2 and inhibit its activities, therefore enabling the mTOR signaling pathway. Sustained activation of mTORC1 blocks growth factor signaling through the activation of negative loops that inhibit PI3-kinase (PI3K) signaling [101]. The activation of mTORC1 promotes protein synthesis mainly by phosphorylating the kinase S6K and through the regulator of translation 4E-BP1 [102]. The biogenesis of lipids is induced through the activation of transcription factors SREBP1 and PPARγ [103]. The active complex mTORC1 promotes anabolism and inhibits catabolism by blocking autophagy through the phosphorylation of a complex that consists of ULK1-Atg13-FIP200 [104].


Adaptive response, evidence of cross-resistance and its potential clinical use.

Milisav I, Poljsak B, Suput D - Int J Mol Sci (2012)

Simplified core stress signaling pathways. The kinase mTOR is a part of complexes mTORC1 and mTORC2. mTORC1 is at the bottom of the PI3-kinase (PI3K) and protein kinase B (AKT) signaling pathways, which receive signals from growth factor receptors at the plasma membrane [55]. mTORC1 also receives signals from p53 through AMPK in the case of DNA damage, through AMPK in the case of energy deficit, through IκB kinase β (IKKβ) during inflammation, etc. [104]. mTORC1 is inhibited by the heterodimer of tuberous sclerosis proteins TSC1 and TSC2 (TSC1/2). Sustained activation of mTORC1 blocks growth factor signaling through activation of the negative loop that inhibits PI3K signaling [101]. The activation of mTORC1 promotes protein synthesis mainly by phosphorylating the kinase S6K and through the regulator of translation 4E-BP1 [102,104]. The biogenesis of lipids is induced through the activation of transcription factors SREBP1 and PPARγ [103]. The energy metabolism is activated through the activation of expression of hypoxia inducing factor 1α (HIF1α) [104]. The active complex mTORC1 promotes anabolism and inhibits catabolism by blocking autophagy through phosphorylation of a complex that consists of ULK1-Atg13-FIP200 and inhibits lysosome biogenesis likely through the transcription factor EB (TFEB) [104]. mTORC2 (not shown) is activated by growth factors and regulates the organization of actin cytoskeleton through protein kinase C-α (PKC-α); it also regulates the serum- and glucocorticoid-induced kinase 1 (SGK1) that controls ion transport and growth; and AKT, which regulates metabolism, survival, apoptosis, growth and proliferation through phosphorylation of several effectors, including TSC1/2 [104].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472714&req=5

f5-ijms-13-10771: Simplified core stress signaling pathways. The kinase mTOR is a part of complexes mTORC1 and mTORC2. mTORC1 is at the bottom of the PI3-kinase (PI3K) and protein kinase B (AKT) signaling pathways, which receive signals from growth factor receptors at the plasma membrane [55]. mTORC1 also receives signals from p53 through AMPK in the case of DNA damage, through AMPK in the case of energy deficit, through IκB kinase β (IKKβ) during inflammation, etc. [104]. mTORC1 is inhibited by the heterodimer of tuberous sclerosis proteins TSC1 and TSC2 (TSC1/2). Sustained activation of mTORC1 blocks growth factor signaling through activation of the negative loop that inhibits PI3K signaling [101]. The activation of mTORC1 promotes protein synthesis mainly by phosphorylating the kinase S6K and through the regulator of translation 4E-BP1 [102,104]. The biogenesis of lipids is induced through the activation of transcription factors SREBP1 and PPARγ [103]. The energy metabolism is activated through the activation of expression of hypoxia inducing factor 1α (HIF1α) [104]. The active complex mTORC1 promotes anabolism and inhibits catabolism by blocking autophagy through phosphorylation of a complex that consists of ULK1-Atg13-FIP200 and inhibits lysosome biogenesis likely through the transcription factor EB (TFEB) [104]. mTORC2 (not shown) is activated by growth factors and regulates the organization of actin cytoskeleton through protein kinase C-α (PKC-α); it also regulates the serum- and glucocorticoid-induced kinase 1 (SGK1) that controls ion transport and growth; and AKT, which regulates metabolism, survival, apoptosis, growth and proliferation through phosphorylation of several effectors, including TSC1/2 [104].
Mentions: As the consequences of stress are alterations in cellular metabolism, growth and division, it is no surprise that the main signaling pathways that regulate cell growth, metabolism, senescence and apoptosis also regulate the stress responses. The complex mTORC1 with its catalytic subunit mTOR regulates growth by maintaining the balance between the anabolic processes, like macromolecular synthesis, and catabolic processes, such as autophagy (Figure 5). mTORC1 mediates cellular responses to many types of stress, like DNA damage and drops in the level of energy, oxygen, amino acids and glucose. mTORC1 is at the bottom of PI3K and AKT signaling pathways, which receive signals from growth factor receptors at the plasma membrane and other inputs [55]. mTORC1 consists of mTOR and regulatory-associated protein of mTOR (raptor), mammalian lethal with Sec13 protein 8 (mLST8), proline-rich AKT substrate 40 kDa (PRAS40), and DEP-domain-containing mTOR-interacting protein (Deptor). The small G protein Rheb in the GTP-bound form stimulates the activity of mTORC1. Rheb is inhibited by the heterodimer of tuberous sclerosis proteins TSC1 and TSC2 (TSC1/2), which convert Rheb into an inactive GDP-bound state. Growth factors promote activities of several kinases, such as AKT, Erk and Rsk, which phosphorylate TSC1/2 and inhibit its activities, therefore enabling the mTOR signaling pathway. Sustained activation of mTORC1 blocks growth factor signaling through the activation of negative loops that inhibit PI3-kinase (PI3K) signaling [101]. The activation of mTORC1 promotes protein synthesis mainly by phosphorylating the kinase S6K and through the regulator of translation 4E-BP1 [102]. The biogenesis of lipids is induced through the activation of transcription factors SREBP1 and PPARγ [103]. The active complex mTORC1 promotes anabolism and inhibits catabolism by blocking autophagy through the phosphorylation of a complex that consists of ULK1-Atg13-FIP200 [104].

Bottom Line: Stress responses are mechanisms used by organisms to adapt to and overcome stress stimuli.Studies have reported life-prolonging effects of a wide variety of so-called stressors, such as oxidants, heat shock, some phytochemicals, ischemia, exercise and dietary energy restriction, hypergravity, etc.These stress responses, which result in enhanced defense and repair and even cross-resistance against multiple stressors, may have clinical use and will be discussed, while the emphasis will be on the effects/cross-effects of oxidants.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, Ljubljana SI-1000, Slovenia; E-Mail: dusan.suput@mf.uni-lj.si ; Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, Ljubljana SI-1000, Slovenia; E-Mail: borut.poljsak@zf.uni-lj.si.

ABSTRACT
Organisms and their cells are constantly exposed to environmental fluctuations. Among them are stressors, which can induce macromolecular damage that exceeds a set threshold, independent of the underlying cause. Stress responses are mechanisms used by organisms to adapt to and overcome stress stimuli. Different stressors or different intensities of stress trigger different cellular responses, namely induce cell repair mechanisms, induce cell responses that result in temporary adaptation to some stressors, induce autophagy or trigger cell death. Studies have reported life-prolonging effects of a wide variety of so-called stressors, such as oxidants, heat shock, some phytochemicals, ischemia, exercise and dietary energy restriction, hypergravity, etc. These stress responses, which result in enhanced defense and repair and even cross-resistance against multiple stressors, may have clinical use and will be discussed, while the emphasis will be on the effects/cross-effects of oxidants.

No MeSH data available.


Related in: MedlinePlus