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PMID:17157356
| Citation |
Ayyadevara, S, Dandapat, A, Singh, SP, Siegel, ER, Shmookler Reis, RJ, Zimniak, L and Zimniak, P (2007) Life span and stress resistance of Caenorhabditis elegans are differentially affected by glutathione transferases metabolizing 4-hydroxynon-2-enal. Mech. Ageing Dev. 128:196-205 |
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| Abstract |
The lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) forms as a consequence of oxidative stress, and acts as a signaling molecule or, at superphysiological levels, as a toxicant. The steady-state concentration of the compound reflects the balance between its generation and its metabolism, primarily through glutathione conjugation. Using an RNAi-based screen, we identified in Caenorhabditis elegans five glutathione transferases (GSTs) capable of catalyzing 4-HNE conjugation. RNAi knock-down of these GSTs (products of the gst-5, gst-6, gst-8, gst-10, and gst-24 genes) sensitized the nematode to electrophilic stress elicited by exposure to 4-HNE. However, interference with the expression of only two of these genes (gst-5 and gst-10) significantly shortened the life span of the organism. RNAi knock-down of the other GSTs resulted in at least as much 4-HNE adducts, suggesting tissue specificity of effects on longevity. Our results are consistent with the oxidative stress theory of organismal aging, broadened by considering electrophilic stress as a contributing factor. According to this extended hypothesis, peroxidation of lipids leads to the formation of 4-HNE in a chain reaction which amplifies the original damage. 4-HNE then acts as an "aging effector" via the formation of 4-HNE-protein adducts, and a resulting change in protein function. |
| Links |
PubMed PMC1819584 Online version:10.1016/j.mad.2006.11.025 |
| Keywords |
Aldehydes/chemistry; Aldehydes/metabolism; Aldehydes/pharmacology; Animals; Caenorhabditis elegans/chemistry; Caenorhabditis elegans/drug effects; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Glutathione Transferase/genetics; Glutathione Transferase/metabolism; Longevity/physiology; RNA Interference; Stress, Psychological |
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