TY - JOUR
T1 - Sex differences in XIAP cleavage after traumatic brain injury in the rat
AU - Bramlett, Helen
AU - Furones-Alonso, Ofelia
AU - Lotocki, George
AU - Rodriguez-Paez, Alejandra
AU - Sanchez-Molano, Juliana
AU - Keane, Robert
PY - 2009/9/8
Y1 - 2009/9/8
N2 - Sex influences histological and behavioral outcomes following traumatic brain injury (TBI), but the underlying sex-dependent pathomechanisms regulating outcome measures remain poorly defined. Here, we investigated the TBI-induced regulation of the X-linked inhibitor of apoptosis protein (XIAP) that, in addition to suppressing cell death by inhibition of caspases, is involved in signaling cascades, including immune regulation and cell migration. Since estrogen has been shown to have anti-apoptotic properties, we specifically examined sex differences and the influence of estrogen on XIAP processing after TBI. Sprague-Dawley male (TBI-M), female (TBI-F), ovariectomized female (TBI-OVX) and ovariectomized females supplemented with estrogen (TBI-OVX + EST) were subjected to moderate (1.7-2.2 atm) fluid percussion (FP) injury. Animals were sacrificed 24 h after FP injury; cortical tissue (ipsilateral and contralateral) was dissected and analyzed for XIAP processing by immunoblot analysis (n = 6-7/group) or confocal microscopy (n = 2-3/group). Significant differences in XIAP cleavage products in the ipsilateral cortex were found between groups (p < 0.03). Post hoc analysis showed an increase in XIAP processing in both TBI-F and TBI-OVX + EST compared to TBI-M and TBI-OVX (p < 0.05), indicating that more XIAP is cleaved following injury in intact females and TBI-OVX + EST than in TBI-M and TBI-OVX groups. Co-localization of XIAP within neurons also demonstrated sex-dependent changes. Based on these data, it appears that the processing of XIAP after injury is different between males and females and may be influenced by exogenous estrogen treatment.
AB - Sex influences histological and behavioral outcomes following traumatic brain injury (TBI), but the underlying sex-dependent pathomechanisms regulating outcome measures remain poorly defined. Here, we investigated the TBI-induced regulation of the X-linked inhibitor of apoptosis protein (XIAP) that, in addition to suppressing cell death by inhibition of caspases, is involved in signaling cascades, including immune regulation and cell migration. Since estrogen has been shown to have anti-apoptotic properties, we specifically examined sex differences and the influence of estrogen on XIAP processing after TBI. Sprague-Dawley male (TBI-M), female (TBI-F), ovariectomized female (TBI-OVX) and ovariectomized females supplemented with estrogen (TBI-OVX + EST) were subjected to moderate (1.7-2.2 atm) fluid percussion (FP) injury. Animals were sacrificed 24 h after FP injury; cortical tissue (ipsilateral and contralateral) was dissected and analyzed for XIAP processing by immunoblot analysis (n = 6-7/group) or confocal microscopy (n = 2-3/group). Significant differences in XIAP cleavage products in the ipsilateral cortex were found between groups (p < 0.03). Post hoc analysis showed an increase in XIAP processing in both TBI-F and TBI-OVX + EST compared to TBI-M and TBI-OVX (p < 0.05), indicating that more XIAP is cleaved following injury in intact females and TBI-OVX + EST than in TBI-M and TBI-OVX groups. Co-localization of XIAP within neurons also demonstrated sex-dependent changes. Based on these data, it appears that the processing of XIAP after injury is different between males and females and may be influenced by exogenous estrogen treatment.
KW - Sex differences
KW - Traumatic brain injury
KW - X-linked inhibitor of apoptosis
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U2 - 10.1016/j.neulet.2009.05.071
DO - 10.1016/j.neulet.2009.05.071
M3 - Article
C2 - 19500649
AN - SCOPUS:67649363281
VL - 461
SP - 49
EP - 53
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -