Cholesterol-producing transgenic Caenorhabditis elegans lives longer due to newly acquired enhanced stress resistance

Eun Young Lee, Yhong Hee Shim, David J. Chitwood, Soon Baek Hwang, Junho Lee, Young Ki Paik

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

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 Δ7 double bond of sterols and is suspected to be defective in C. elegans, in which the major endogenous sterol is 7-dehydrocholesterol (7DHC). We microinjected a human DHCR expression vector into C. elegans, which was then incorporated into chromosome by γ-radiation. This transgenic C. elegans was named cholegans, i.e., cholesterol-producing C. elegans, because it was able to convert 7DHC into cholesterol. We investigated the effects of changes in sterol composition on longevity and stress resistance by examining brood size, mean life span, UV resistance, and thermotolerance. Cholegans contained 80% more cholesterol than the wild-type control. The brood size of cholegans was reduced by 40% compared to the wild-type control, although the growth rate was not significantly changed. The mean life span of cholegans was increased up to 131% in sterol-deficient medium as compared to wild-type. The biochemical basis for life span extension of cholegans appears to partly result from its acquired resistance against both UV irradiation and thermal stress.

Original languageEnglish
Pages (from-to)929-936
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume328
Issue number4
DOIs
Publication statusPublished - 2005 Mar 25

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (03-PJ10-PG6-GP01-002 to Y.K.P.), and by a grant of the Basic Research program of the Korea Science and Engineering Foundation (R04-2002-000-20096-0 (2004) to Y.H.S.), Seoul, Korea. Nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health Center for Research Resources.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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