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Title: CHOLESTEROL-PRODUCING TRANSGENIC CAENORHABDITIS ELEGANS LIVES LONGER BECAUSE OF ENHANCED STRESS RESISTANCE

Author
item LEE, EUN-YOUNG - YONSEI UNIV, S. KOREA
item SHIM, YHONG-HEE - KONKUK UNIV, S. KOREA
item Chitwood, David
item HWANG, SOON - SEOUL NATL UNIV, S. KOREA
item LEE, JUNHO - SEOUL NATL UNIV, S. KOREA
item PAIK, YOUNG-KI - YONSEI UNIV, S. KOREA

Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2005
Publication Date: 2/1/2005
Citation: Lee, E., Shim, Y., Chitwood, D.J., Hwang, S.B., Lee, J., Paik, Y., Cholesterol-producing transgenic Caenorhabditis elegans lives longer because of enhanced stress resistance. 2005. Biochem. Biophys. Res. Commun. 328: 929-936.

Interpretive Summary: Because Caenorhabditis elegans lacks several components of the de novo sterol biosynthetic pathway, it requires sterol as an essential nutrient. Supplemented cholesterol undergoes extensive enzymatic modification in C. elegans to form other sterols of unknown function. 7-Dehydrocholesterol reductase (DHCR) catalyzes the reduction of the delta-7 double bond of sterols and is suspected to be absent in C. elegans, in which the major endogenous sterol is 7-dehydrocholesterol. We microinjected a human DHCR expression vector into C. elegans, which was incorporated into chromosome I by gamma irradiation. This transgenic C. elegans was named cholegans, i.e., cholesterol producing C. elegans, because it was able to convert 7-dehydrocholesterol into cholesterol. We investigated the effects of changes in sterol composition on longevity and stress resistance by examining brood size, mean life span, thermotolerance and ultraviolet light resistance. The brood size of cholegans grown in the presence of cholesterol was reduced by 40% compared to N2 controls, while male mating efficiency increased 145%; growth rate was not significantly changed. The mean life span of cholegans increased by as much as 131% in the absence of sterol as compared to N2. The biochemical basis for life span expansion of cholegans appears to be in part its acquired stress resistance against both UV irradiation and thermal stimuli.

Technical Abstract: Because Caenorhabditis elegans lacks several components of the de novo sterol biosynthetic pathway, it requires sterol as an essential nutrient. Supplemented cholesterol undergoes extensive enzymatic modification in C. elegans to form other sterols of unknown function. 7-Dehydrocholesterol reductase (DHCR) catalyzes the reduction of the delta-7 double bond of sterols and is suspected to be absent in C. elegans, in which the major endogenous sterol is 7-dehydrocholesterol. We microinjected a human DHCR expression vector into C. elegans, which was incorporated into chromosome I by gamma irradiation. This transgenic C. elegans was named cholegans, i.e., cholesterol producing C. elegans, because it was able to convert 7-dehydrocholesterol into cholesterol. We investigated the effects of changes in sterol composition on longevity and stress resistance by examining brood size, mean life span, thermotolerance and ultraviolet light resistance. The brood size of cholegans grown in the presence of cholesterol was reduced by 40% compared to N2 controls, while male mating efficiency increased 145%; growth rate was not significantly changed. The mean life span of cholegans increased by as much as 131% in the absence of sterol as compared to N2. The biochemical basis for life span expansion of cholegans appears to be in part its acquired stress resistance against both UV irradiation and thermal stimuli.