INVESTIGADORES
MILANESI Lorena Magdalena
congresos y reuniones científicas
Título:
The Antiapoptotic Action of 17beta-Estradiol in Skeletal Muscle Cells Involves ERK 1/2, p38 MAPK, ASK-1 and HSP27
Autor/es:
ANA C RONDA; NOELIA ZANETTI; ANDREA VASCONSUELO; LORENA MILANESI; ANA RUSSO DE BOLAND; RICARDO BOLAND
Lugar:
Canada
Reunión:
Congreso; 30th Annual Meeting of the American Society for Bone and Mineral research.; 2008
Institución organizadora:
ASBMR
Resumen:
SU185
The Antiapoptotic Action of 17â-Estradiol in Skeletal Muscle Cells
Involves ERK 1/2, p38 MAPK, ASK-1 and HSP27. A. C. Ronda*, N.
Zanetti*, A. Vasconsuelo*, L. Milanesi*, A. Russo de Boland*, R. L. Boland.
Dept. Biologia, Bioquimica & Farmacia, Universidad Nacional del Sur, Bahia
Blanca, Argentina.
Estrogens exert antiapoptotic effects in various cell types, e.g. vascular endothelial,
smooth muscle and breast cancer cells. We have previously reported that 17â-estradiol
inhibits apoptosis through estrogen receptors with non-nuclear localization, e.g.
mitochondria and endoplasmic reticulum, in the mouse skeletal muscle C2C12 cell line.
The steroid hormone abrogates DNA damage, PARP cleavage and cytochrome c release
induced by H2O2 or etoposide. This mechanism involves fast activation of the PI3K/Akt/
Bad pathway. It was demonstrated that the estrogen also triggers rapid phosphorylation of
ERK 1/2 and p38 MAPK. Using specific inhibitors it was shown that both MAPKs mediate
the effects of estradiol on Akt and Bad phosphorylation, cytochrome c and Smac/Diablo
release, caspase 3 and PARP cleavage, and morphological changes of the cells.
Interestingly, we found that ERK1/2 activated by 17â-estradiol is located mainly in
mitochondria. Parallel studies showed that the interaction between proapoptotic kinase
ASK-1 with phospho-Akt increases in presence of estrogen. This fact suggests another
possible point of negative regulation of the apoptotic cascade by Akt. Furthermore,
evidence was obtained that 17â-estradiol at longer exposure times increases the expression
of HSP27. Assays under apoptotic conditions linked this chaperone to the protective action
of the hormone, specifically regulating caspase-3 activity. Immunocytochemistry and coimmunoprecipitation
assays revealed interaction of HSP27 and ER â in mitochondria.
Altogether, these data imply that ERK 1/2, p38 MAPK, ASK-1 and HSP27 play a role in
the mechanism underlying the antiapoptotic action of 17â-estradiol in skeletal muscle
cells.
Disclosures: R.L. Boland, None.