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The
aryl hydrocarbon receptor (AhR) is a ubiquitously expressed,
ligand-activated transcription factor. Its’ ligand-dependent
activities influence processes involved in xenobiotic
metabolism, immune function, development, cell cycle
progression, and cell death. The Reiners laboratory is
interested in: 1) the signaling processes that regulate AhR
function; 2) AhR regulation of cholesterol trafficking and
homeostasis; and the 3) ligand-independent functions of the
AhR. With regards to the latter, particular attention is
focused on how the AhR regulates lysosome fragility, and
susceptibilities to subclasses of cytotoxic agents.
Although the term ‘death’ has negative connotations, it is a
normal physiological process and necessary for maintenance
of homeostasis. Indeed, cancer is often a consequence of
defective cell death pathways. The Reiners laboratory is
interested in understanding the processes of programmed cell
death, and determining how insults to specific organelles (lysosomes,
endoplasmic reticulum, nucleus, mitochondria) initiate death
pathways. Such information has significant therapeutic
application. |
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Caruso JA, Mathieu PA, Reiners Jr JJ. Sphingomyelins
suppress the targeted disruption of lysosomes / endosomes
and the induction of apoptosis by the lysosomal
photosensitizer NPe6 in photodynamic therapy protocols.
Biochem J. 2005 June 8; [Epub ahead of print] PMID: 15943580
Kessel D., Conley M, Vincete MG, Reiners Jr JJ. Studies on
the subcellular localization of the porphycene CPO.
Photochem. Photbiol. 2005 May-Jun;81(3):153-63. PMID
15745423
Reiners JJ Jr, Kessel D. Susceptibility of myelomonocytic
leukemia U937 cells to the induction of apoptosis by the
non-peptidic Bcl-2 ligand HA14-1 is cell cycle
phase-dependent. Cancer Lett. 2005 Apr 28;221(2):153-63.
PMID: 15808401
Kessel D, Castelli M, Reiners JJ. Ruthenium red-mediated
suppression of Bcl-2 loss and Ca(2+) release initiated by
photodamage to the endoplasmic reticulum: scavenging of
reactive oxygen species. Cell Death Differ. 2005
May;12(5):502-11. PMID: 15719027
Joiakim A, Mathieu PA, Elliott AA, Reiners JJ Jr.
Superinduction of CYP1A1 in MCF10A cultures by
cycloheximide, anisomycin, and puromycin: a process
independent of effects on protein translation and unrelated
to suppression of aryl hydrocarbon receptor proteolysis by
the proteasome. Mol Pharmacol. 2004 Oct;66(4):936-47. PMID:
15385644
Castelli M, Reiners JJ, Kessel D. A mechanism for the
proapoptotic activity of ursodeoxycholic acid: effects on
Bcl-2 conformation. Cell Death Differ. 2004
Aug;11(8):906-14. PMID: 15258617
Caruso JA, Mathieu PA, Joiakim A, Leeson B, Kessel D, Sloane
BF, Reiners JJ Jr. Differential susceptibilities of murine
hepatoma 1c1c7 and Tao cells to the lysosomal
photosensitizer NPe6: influence of aryl hydrocarbon receptor
on lysosomal fragility and protease contents. Mol Pharmacol.
2004 Apr;65(4):1016-28. PMID: 15044632
Joiakim A, Mathieu PA, Palermo C, Gasiewicz TA, Reiners JJ
Jr. The Jun N-terminal kinase inhibitor SP600125 is a
ligand and antagonist of the aryl hydrocarbon receptor. Drug
Metab Dispos. 2003 Nov;31(11):1279-82. PMID: 14570754
Mattingly RR, Gibbs RA, Menard RE, Reiners JJ Jr. Potent
suppression of proliferation of a10 vascular smooth muscle
cells by combined treatment with lovastatin and
3-allylfarnesol, an inhibitor of protein farnesyltransferase.
J Pharmacol Exp Ther. 2002 Oct;303(1):74-81. PMID: 12235235
Reiners JJ Jr, Caruso JA, Mathieu P, Chelladurai B, Yin XM,
Kessel D. Release of cytochrome c and activation of
pro-caspase-9 following lysosomal photodamage involves Bid
cleavage. Cell Death Differ. 2002 Sep;9(9):934-44. PMID:
12181744 |