Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10796036 | Biochimica et Biophysica Acta (BBA) - Bioenergetics | 2008 | 14 Pages |
Abstract
Nonenzymatic molecular modifications induced by reactive carbonyl species (RCS) generated by peroxidation of membrane phospholipids acyl chains play a causal role in the aging process. Most of the biological effects of RCS, mainly α,β-unsaturated aldehydes, di-aldehydes, and keto-aldehydes, are due to their capacity to react with cellular constituents, forming advanced lipoxidation end-products (ALEs). Compared to reactive oxygen and nitrogen species, lipid-derived RCS are stable and can diffuse within or even escape from the cell and attack targets far from the site of formation. Therefore, these soluble reactive intermediates, precursors of ALEs, are not only cytotoxic per se, but they also behave as mediators and propagators of oxidative stress and cellular and tissue damage. The consequent loss-of-function and structural integrity of modified biomolecules can have a wide range of downstream functional consequences and may be the cause of subsequent cellular dysfunctions and tissue damage. The causal role of ALEs in aging and longevity is inferred from the findings that follow: a) its accumulation with aging in several tissues and species; b) physiological interventions (dietary restriction) that increase longevity, decrease ALEs content; c) the longer the longevity of a species, the lower is the lipoxidation-derived molecular damage; and finally d) exacerbated levels of ALEs are associated with pathological states.
Keywords
GFAPMDAPHGPxERKNF-kBHSPsSAMGPXGSTGSHCBPDBINrf2TKRAKRRCSPDGFRCREBEGFRALDH4-HHEEPAJnk2-Hydroxyheptanal4-HNESREBPMolecular damageHsfsLongevity4-Hydroxyhexenal4-hydroxy-trans-2-nonenalkeap1c-Jun N-terminal kinaseMAPKROSUCPsaldehyde dehydrogenaseUnsaturated aldehydealdo-keto reductaseArachidonic acidEicosapentaenoic aciddocosahexaenoic acidLinoleic acidPolyunsaturated fatty acidPUFALipid oxidationALEsUncoupling proteinsDHAFree radicalRONSAgingSODSuperoxide dismutasedouble bond indexPeroxidizability indexantioxidant response elementNuclear factor-kBLipoxidationmalondialdehydecaloric restrictionadvanced lipoxidation end-productMitochondriaARECREB-binding proteinSterol regulatory element-binding proteinGlial fibrillary acidic proteinHeat-shock proteinsmitogen-activated protein kinaseextracellular signal-regulated kinaseGlutathioneglutathione-S-transferaseglutathione peroxidasereactive nitrogen speciesreactive carbonyl speciesReactive oxygen speciesplatelet-derived growth factor receptorEpidermal growth factor receptortyrosine kinase receptorsONE
Related Topics
Life Sciences
Agricultural and Biological Sciences
Plant Science
Authors
Reinald Pamplona,