Characterization of Recombinant TL-PST with Minoxidil
and Dopamine.
Patrick Kudlacek, Dahn L. Clemens, and Robert
J. Anderson. (1995) Biochem.
Biophys. Res. Comm. 210: 363-369.
Establishment of a Recombinant Hepatic Cell Line
Stably Expressing Alcohol
Dehydrogenase. Dahn L. Clemens, Christine M.
Halgard, Rodney M. Miles,
Michael F. Sorrell and Dean J. Tuma. (1995) Arch.
Biochem. Biophys. 312: 311
318.
Impairment of the Asialoglycoprotein Receptor by
Ethanol Oxidation.
Dahn L.Clemens, Christine M. Halgard, Jack, R.
Cole, Rodney M. Miles,
Michael F. Sorrell and Dean J. Tuma. (1996) Biochem.
Pharm. 52: 1499-1505.
Characterization of recombinant human liver
dehydroepiandrosterone sulfotransferase with minoxidil as the substrate.
Patrick Kudlacek, Dahn L. Clemens, Christine M. Halgard and Robert J.
Anderson. (1997) Biochem. Pharm. 53: 215-221.
Ethanol Oxidation Mediates Impaired Hepatic Receptor
Mediated Endocytosis.
Dahn L. Clemens, Carol A. Casey, Dean J. Tuma.
(1998) Alcoholism Clin. Exp.
Res. 22: 778-779.
Sulfation of Minoxidil by Multiple Human Cytosolic
Sulfotransferase. Robert J. Anderson, Patrich Kudlacek, and Dahn L.
Clemens. (1998) Chemico-Biol. 109: 53-67.
Sulfation of Idothyronines by Human Sulfotransferase 1C1
(SULT1C1), Xinying Li, Dahn L. Clemens, and Robert Anderson. (2000)
Biochemical. Pharmacology 60:1713-1716
Use of Cultured cells in Assessing Ethanol Toxicity and
Ethanol-Related Metabolism. Terrence M. Donohue Jr., Dahn L.
Clemens, Andrea Galli, David Crabb, Natalia Nieto, Junji Kato, and
Shirish Brave (2001) Alcoholism Clin. Exp. Res. 25: 87S-93S
Ethanol inhibits the JAK-STAT signaling pathway in freshly isolated
rat hepatocytes but not in cultured hepatocytes or HepG2 cells: evidence
for a lack of involvement of ethanol metabolism. Jianping Chen,
Dahn L. Clemens, Arthur I. Cederbaum, and Bin Gao. (2001) Clinical
Biochemistry 34: 203-209
Characterization of Human liver Thermostable Phenol Sulfotransferase
(SULT1A1) Allozymes with 3,3’,5-Triiodothyronine as the Substrate.
Xinying Li, Dahn L. Clemens, and Robert Anderson. (2001) J.
Endocrinology, In Press.
Relationship between Acetaldehyde Levels and Cell Survival in Ethanol
Metabolizing Hepatoma Cells. Dahn L. Clemens, Andrew Forman,
Thomas R. Jerrells, Michael F. Sorrell, and Dean J. Tuma. (2001)
Hepatology. Submitted:
AKT
Proto-Oncogen Overexpression is an Early Event During Sporadic Colon
Carcinogenesis. Hemant K.
Roy, Bola F. Olusola, Dahn L. Clemens, William J. Karolski, Ann Ratashak,
Henny J. lynch, Thomas C. Smyrk. (2001) Carcinogenesis.
In Press
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Cultured hepatocytes rapidly lose the ability to express
alcohol dehydrogenase and thus, the ability to efficiently oxidize ethanol.
Therefore, it has been difficult to investigate the mechanisms, in vitro by
which chronic ethanol oxidation damages cells. By stably transfecting the
hepatocellular carcinoma cell line, Hep G2, with an expression vector
containing a cDNA encoding murine alcohol dehydrogenase, we have constructed
a number of clonal recombinant cell lines, designated VA cells, that
constitutively express alcohol dehydrogenase. These cell lines oxidize
ethanol, which results in the production and accumulation of acetaldehyde,
and a dramatic change in the NADH/NAD+ ratio (redox-state) in the cells.
Initially, we observed that culturing VA cells in the presence of ethanol
resulted in a dramatic reduction in cell accumulation. This reduction could
be overcome by inhibiting alcohol dehydrogenase activity, demonstrating that
it was mediated by ethanol oxidation. Further investigation revealed that
this ethanol oxidation-mediated reduction in cell accumulation was at least
partially due to impaired DNA synthesis. It is believed that production of
acetaldehyde, and the change in redox-state of hepatocytes, could be
responsible for many of the dysfunctions associated with alcoholic liver
disease. Therefore, using the VA cells we propose to investigate the roles
of these two changes in the ethanol-induced impairment of DNA synthesis.
Because these changes occur simultaneously, it has been difficult to
differentiate between the effects of each of these changes. Using the VA
cells we have been able to differentiate between the effects of acetaldehyde
and redox change. Alcohol dehydrogenase-mediated oxidation of ethanol
results in the production of acetaldehyde and a redox-shift. Conversely, the
oxidation of isopropanol requires NAD+ as a cofactor and causes a redox-shift
but does not result in the production of acetaldehyde. Therefore, by
comparing the results obtained from cells cultured in either ethanol or
isopropanol, we have been able to determine the role of these two changes in
the impairment of DNA synthesis. Understanding the consequences of specific
cellular changes caused by ethanol oxidation could provide valuable
information regarding the onset and progression of alcoholic liver disease.
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