TY - JOUR
T1 - Inhibition of apoptotic potency by ligand stimulated thyroid hormone receptors located in mitochondria
AU - Saelim, Nuttawut
AU - Holstein, Deborah
AU - Chocron, Estrella S.
AU - Camacho, Patricia
AU - Lechleiter, James Donald
N1 - Funding Information:
Acknowledgements We wish to thank Erin Manitou and the Electron Microscopy Pathology Core and Victoria Centonze Frohlich and the Imaging Core Facility at UTHSCSA. Financial support: This work was supported by National Institutes of Health Grant R01 GM48451 and PO1 AG19316.
PY - 2007/10
Y1 - 2007/10
N2 - We recently reported that shortened thyroid hormone receptor isoforms (TRs) can target mitochondria and acutely modulate inositol 1,4,5 trisphosphate (IP3)-mediated Ca2+ signaling when activated by thyroid hormone 3,5,3′-tri-iodothyronine (T3). Stimulation occurs via an increase in mitochondrial metabolism that is independent of transcriptional activity. Here, we present evidence that T3-bound xTR βA1s inhibit apoptotic activity mediated by cytochrome c release. An assay for apoptotic potency was modified to measure the ability of Xenopus oocyte extracts to induce morphological changes in isolated liver nuclei. Apoptotic potency was significantly decreased when oocyte extract was prepared from xTRβA1 expressing oocytes and treated with T 3. The ability of T3 treatment to inhibit apoptosis was dependent on the expression of xTRβA1s in the mitochondrial fraction, not in the cytosolic fraction. T3 treatment also increased the membrane potential of isolated mitochondria prepared from oocytes expressing xTRβA1s but not from wildtype controls. We conclude that T 3 acutely regulates cytochrome c release in a potential dependent manner by activating TRs located within mitochondria.
AB - We recently reported that shortened thyroid hormone receptor isoforms (TRs) can target mitochondria and acutely modulate inositol 1,4,5 trisphosphate (IP3)-mediated Ca2+ signaling when activated by thyroid hormone 3,5,3′-tri-iodothyronine (T3). Stimulation occurs via an increase in mitochondrial metabolism that is independent of transcriptional activity. Here, we present evidence that T3-bound xTR βA1s inhibit apoptotic activity mediated by cytochrome c release. An assay for apoptotic potency was modified to measure the ability of Xenopus oocyte extracts to induce morphological changes in isolated liver nuclei. Apoptotic potency was significantly decreased when oocyte extract was prepared from xTRβA1 expressing oocytes and treated with T 3. The ability of T3 treatment to inhibit apoptosis was dependent on the expression of xTRβA1s in the mitochondrial fraction, not in the cytosolic fraction. T3 treatment also increased the membrane potential of isolated mitochondria prepared from oocytes expressing xTRβA1s but not from wildtype controls. We conclude that T 3 acutely regulates cytochrome c release in a potential dependent manner by activating TRs located within mitochondria.
KW - Apoptosis assay
KW - Confocal microscopy
KW - Steroid receptors
KW - Xenopus oocytes
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U2 - 10.1007/s10495-007-0109-1
DO - 10.1007/s10495-007-0109-1
M3 - Article
C2 - 17701361
AN - SCOPUS:34848834197
SN - 1360-8185
VL - 12
SP - 1781
EP - 1794
JO - Apoptosis
JF - Apoptosis
IS - 10
ER -