Submitted on January 12, 2006
Revised on February 10, 2006
Accepted on February 27, 2006
Identification of a novel sulfonated oxysterol, 5-cholesten-3
, 25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria
Shunlin Ren, Phillip Hylemon, Zong-Ping Zhang, Daniel Rodriguez-Agudo, Dalila Marques, Xiaobo Li, Huiping Zhou, Gregorio Gil, and William Pandak
Medicine Dept., McGuire VA Medical Center, Richmond, VA 23249
Corresponding Author: shunlin.ren{at}va.gov
The present study depicts the discovery of a novel sulfonated oxysterol and dramatic increases of its levels in the mitochondria and in the nuclei following overexpression of StarD1 in primary rat hepatocytes. Forty-eight hours after infection of primary rat hepatocytes with recombinant adenovirus encoding the mitochondria cholesterol transport protein (StarD1), rates of bile acid synthesis increased by 5-fold. Concurrently, [14C]oxysterol derivatives were dramatically increased both in the mitochondria and in the nuclei of StarD1 overexpressing cells, but not in culture media. A presumed oxysterol product after sulfatase treatment was identified as 25-hydroxycholesterol, suggesting the nuclear oxysterol could be a sulfonated 25-hydroxycholesterol. MS/MS analysis characterized the nuclear oxysterol as 5-cholesten-3, 25-diol 3-sulphate. Adding to the physiological relevance, this oxysterol was found in low concentrations in the nuclei of normal human liver tissues. We hypothesized a new pathway by which a novel nuclear sulfonated oxysterol is generated in the mitochondria and translocated to the nucleus.
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