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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

Pathways to remove stress-damaged macromolecules. The two major degradation pathways in eukaryotes are the ubiquitin-proteasome pathway (UPP) and autophagy. UPP is the degradation pathway for soluble proteins. In response to oxidative stress, it degrades oxidized proteins [15]. Through degradation of the transcription factor nuclear factor-E2-related factor 2 (Nrf2) that is involved in the transcriptional regulation of antioxidant enzymes, the UPP participates in the regulation of the intracellular redox status [41,42]. Autophagy is the name for several degradation pathways. Its best-described form is macroautophagy, the non-selective process of engulfment of cellular material into double membrane vesicles, which are delivered to lysosomes for degradation [43,44]. It has been recently appreciated that autophagy is also selective, called selective autophagy, in which the cargo is recognized by adaptor proteins [45]. Tiny portions of cytoplasm are sequestered and subsequently engulfed by lysosomes in microautophagy [46,47]. This process is well known in yeasts, however, there are not enough data on the mechanisms and physiological relevance of the mammalian microautophagy so far [46]. Chaperone-mediated autophagy (CMA), described only in mammals, delivers selected proteins into lysosomes through specific receptors [48].
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f2-ijms-13-10771: Pathways to remove stress-damaged macromolecules. The two major degradation pathways in eukaryotes are the ubiquitin-proteasome pathway (UPP) and autophagy. UPP is the degradation pathway for soluble proteins. In response to oxidative stress, it degrades oxidized proteins [15]. Through degradation of the transcription factor nuclear factor-E2-related factor 2 (Nrf2) that is involved in the transcriptional regulation of antioxidant enzymes, the UPP participates in the regulation of the intracellular redox status [41,42]. Autophagy is the name for several degradation pathways. Its best-described form is macroautophagy, the non-selective process of engulfment of cellular material into double membrane vesicles, which are delivered to lysosomes for degradation [43,44]. It has been recently appreciated that autophagy is also selective, called selective autophagy, in which the cargo is recognized by adaptor proteins [45]. Tiny portions of cytoplasm are sequestered and subsequently engulfed by lysosomes in microautophagy [46,47]. This process is well known in yeasts, however, there are not enough data on the mechanisms and physiological relevance of the mammalian microautophagy so far [46]. Chaperone-mediated autophagy (CMA), described only in mammals, delivers selected proteins into lysosomes through specific receptors [48].

Mentions: There are two major degradation pathways in eukaryotic cells for removal of stress-damaged components: the ubiquitin-proteasome pathway (UPP) and autophagy (Figure 2). The UPP is the main pathway for degradation of soluble proteins, mainly in the cytosol. The UPP has been recognized recently to respond to oxidative stress and has a role in the degradation of oxidized proteins [15]. In the simplest form, UPP consists of labeling the protein target for degradation by covalent attachment of several molecules of a peptide ubiquitin and its degradation by cytoplasmic complex 26S proteasome. The 26S proteasome consists of a barrel-shaped catalytic core, also called 20S [16]. Two 19S regulatory particles (PA700) bind at either ends of the 20S cylinder and act as a gatekeeper for substrate entry. The ATPase subunits of PA700 contribute to unfolding of the protein substrates and delivery into the proteolytic chamber of 20S [17]. Other subunits of PA700 deubiquitinate the target proteins, or recruit polyubiquitinated substrates to the proteasome. Some proteins, including oxidized proteins, are degraded by the 20S proteasome in an ATP-independent and ubiquitin-independent manner [18–22]. Although many papers report the degradation of oxidized proteins in an ubiquitin-independent manner [18,20,23–29], there are also reports of degradation of ubiquitinated oxidized proteins [30–36]. Proteasome has an important role in selective degradation of oxidized proteins, however how the proteasome distinguishes oxidized proteins from the native ones remains to be determined. Sometimes the oxidation of specific residues results in changes in secondary, tertiary even quaternary structures of the proteins or even results in partial unfolding of the protein [28,37–40]. Such proteins may be recognized by molecular chaperones in a similar manner to other missfolded proteins [37]. The capacity of UPP to degrade proteins is altered by the cellular redox status. A mild to moderate oxidative stress promotes intracellular protein degradation by increasing susceptibility of proteins to degradation and enhancing the proteolytic capacity. Sustained oxidative stress inactivates proteasome without inhibiting the ubiquitination and results in accumulation of ubiquitin conjugates in the cells. Extensive oxidative stress inactivates the proteasome and inhibits the ubiquitination, resulting in accumulation of oxidatively damaged proteins [15].


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

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

Pathways to remove stress-damaged macromolecules. The two major degradation pathways in eukaryotes are the ubiquitin-proteasome pathway (UPP) and autophagy. UPP is the degradation pathway for soluble proteins. In response to oxidative stress, it degrades oxidized proteins [15]. Through degradation of the transcription factor nuclear factor-E2-related factor 2 (Nrf2) that is involved in the transcriptional regulation of antioxidant enzymes, the UPP participates in the regulation of the intracellular redox status [41,42]. Autophagy is the name for several degradation pathways. Its best-described form is macroautophagy, the non-selective process of engulfment of cellular material into double membrane vesicles, which are delivered to lysosomes for degradation [43,44]. It has been recently appreciated that autophagy is also selective, called selective autophagy, in which the cargo is recognized by adaptor proteins [45]. Tiny portions of cytoplasm are sequestered and subsequently engulfed by lysosomes in microautophagy [46,47]. This process is well known in yeasts, however, there are not enough data on the mechanisms and physiological relevance of the mammalian microautophagy so far [46]. Chaperone-mediated autophagy (CMA), described only in mammals, delivers selected proteins into lysosomes through specific receptors [48].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ijms-13-10771: Pathways to remove stress-damaged macromolecules. The two major degradation pathways in eukaryotes are the ubiquitin-proteasome pathway (UPP) and autophagy. UPP is the degradation pathway for soluble proteins. In response to oxidative stress, it degrades oxidized proteins [15]. Through degradation of the transcription factor nuclear factor-E2-related factor 2 (Nrf2) that is involved in the transcriptional regulation of antioxidant enzymes, the UPP participates in the regulation of the intracellular redox status [41,42]. Autophagy is the name for several degradation pathways. Its best-described form is macroautophagy, the non-selective process of engulfment of cellular material into double membrane vesicles, which are delivered to lysosomes for degradation [43,44]. It has been recently appreciated that autophagy is also selective, called selective autophagy, in which the cargo is recognized by adaptor proteins [45]. Tiny portions of cytoplasm are sequestered and subsequently engulfed by lysosomes in microautophagy [46,47]. This process is well known in yeasts, however, there are not enough data on the mechanisms and physiological relevance of the mammalian microautophagy so far [46]. Chaperone-mediated autophagy (CMA), described only in mammals, delivers selected proteins into lysosomes through specific receptors [48].
Mentions: There are two major degradation pathways in eukaryotic cells for removal of stress-damaged components: the ubiquitin-proteasome pathway (UPP) and autophagy (Figure 2). The UPP is the main pathway for degradation of soluble proteins, mainly in the cytosol. The UPP has been recognized recently to respond to oxidative stress and has a role in the degradation of oxidized proteins [15]. In the simplest form, UPP consists of labeling the protein target for degradation by covalent attachment of several molecules of a peptide ubiquitin and its degradation by cytoplasmic complex 26S proteasome. The 26S proteasome consists of a barrel-shaped catalytic core, also called 20S [16]. Two 19S regulatory particles (PA700) bind at either ends of the 20S cylinder and act as a gatekeeper for substrate entry. The ATPase subunits of PA700 contribute to unfolding of the protein substrates and delivery into the proteolytic chamber of 20S [17]. Other subunits of PA700 deubiquitinate the target proteins, or recruit polyubiquitinated substrates to the proteasome. Some proteins, including oxidized proteins, are degraded by the 20S proteasome in an ATP-independent and ubiquitin-independent manner [18–22]. Although many papers report the degradation of oxidized proteins in an ubiquitin-independent manner [18,20,23–29], there are also reports of degradation of ubiquitinated oxidized proteins [30–36]. Proteasome has an important role in selective degradation of oxidized proteins, however how the proteasome distinguishes oxidized proteins from the native ones remains to be determined. Sometimes the oxidation of specific residues results in changes in secondary, tertiary even quaternary structures of the proteins or even results in partial unfolding of the protein [28,37–40]. Such proteins may be recognized by molecular chaperones in a similar manner to other missfolded proteins [37]. The capacity of UPP to degrade proteins is altered by the cellular redox status. A mild to moderate oxidative stress promotes intracellular protein degradation by increasing susceptibility of proteins to degradation and enhancing the proteolytic capacity. Sustained oxidative stress inactivates proteasome without inhibiting the ubiquitination and results in accumulation of ubiquitin conjugates in the cells. Extensive oxidative stress inactivates the proteasome and inhibits the ubiquitination, resulting in accumulation of oxidatively damaged proteins [15].

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