Ethanol influences on Bax associations with mitochondrial membrane proteins in neonatal rat cerebellum.
Ethanol influences on Bax associations with mitochondrial membrane proteins in neonatal rat cerebellum.
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DOI：
10.1002/dneu.22042
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发表时间：
2013-02
影响因子：
3
通讯作者：
Madorsky, Vladimir
中科院分区：
文献类型：
--
作者：
Heaton, Marieta Barrow;Siler-Marsiglio, Kendra;Paiva, Michael;Kotler, Alexandra;Rogozinski, Jonathan;Kubovec, Stacey;Coursen, Mary;Madorsky, Vladimir
这些研究考察了乙醇暴露后新生大鼠小脑线粒体膜上的相互作用，重点研究了促凋亡的Bax与线粒体膜内外膜通透性转换孔(PTP)、电压依赖性阴离子通道(VDAC)和腺嘌呤核苷酸转运体(ANT)蛋白的相互作用。培养的小脑颗粒细胞被用来评估这些相互作用在乙醇神经毒性中的作用。在小脑乙醇易损性最大的年龄(P4)与相对抵抗的较晚年龄(P7)进行分析，以确定这些分子相互作用的差异是否反映了不同的乙醇敏感性。我们发现，在酒精暴露后，BAX与VDAC和ANT的促凋亡关联都增加了，特别是在对乙醇更敏感的年龄，这些相互作用在暴露后至少两小时内一直保持。由于Bax：VDAC的相互作用破坏了VDAC与线粒体己糖激酶(HXK)的保护性相互作用，我们还评估了乙醇处理后VDAC：HXK的相关性，发现乙醇处理可以改变这种相互作用，但只有在暴露后2小时，而且只在P4，乙醇敏感的小脑中。通过药物抑制VDAC和ANT与Bax的相互作用，可以消除培养神经元标本中的乙醇神经毒性，但Bax通道阻滞剂不能。因此，我们得出结论，在这个年龄，在我们的实验模型的限制下，Bax诱导的乙醇损伤后的凋亡级联的主要模式涉及与PTP复合体的蛋白质的相互作用，而不是独立于PTP成分的通道形成。
These studies investigated interactions taking place at the mitochondrial membrane in neonatal rat cerebellum following ethanol exposure, and focused on interactions between pro-apoptotic Bax and proteins of the permeability transition pore (PTP), voltage-dependent anion channel (VDAC), and adenine nucleotide translocator (ANT), of the outer and inner mitochondrial membranes, respectively. Cultured cerebellar granule cells were used to assess the role of these interactions in ethanol neurotoxicity. Analyses were made at the age of maximal cerebellar ethanol vulnerability (P4), compared to the later age of relative resistance (P7), to determine whether differential ethanol sensitivity was mirrored by differences in these molecular interactions. We found that following ethanol exposure, Bax pro-apoptotic associations with both VDAC and ANT were increased, particularly at the age of greater ethanol sensitivity, and these interactions were sustained at this age for at least two hours post-exposure. Since Bax:VDAC interactions disrupt protective VDAC interactions with mitochondrial hexokinase (HXK), we also assessed VDAC:HXK associations following ethanol treatment, and found such interactions were altered by ethanol treatment, but only at two-hours post-exposure, and only in the P4, ethanol-sensitive cerebellum. Ethanol neurotoxicity in cultured neuronal preparations was abolished by pharmacological inhibition of both VDAC and ANT interactions with Bax, but not by a Bax channel blocker. Therefore, we conclude that at this age, within the constraints of our experimental model, a primary mode of Bax-induced initiation of the apoptosis cascade following ethanol insult involves interactions with proteins of the PTP complex, and not channel formation independent of PTP constituents.
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影响因子：
8
作者：
de la Monte, SM;Wands, JR
通讯作者：
Wands, JR
DOI：
10.1111/j.1530-0277.1993.tb00808.x
发表时间：
1993-06-01
影响因子：
3.2
作者：
HAMRE, KM;WEST, JR
通讯作者：
WEST, JR
影响因子：
16.2
作者：
ANKARCRONA, M;DYPBUKT, JM;NICOTERA, P
通讯作者：
NICOTERA, P
DOI：
10.1016/j.molbrainres.2004.06.034
发表时间：
2004-10-22
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Ge, Y;Belcher, SA;Light, KE
通讯作者：
Light, KE
DOI：
10.1111/j.1530-0277.2003.tb04402.x
发表时间：
2003-04-01
影响因子：
3.2
作者：
Heaton, MB;Moore, DB;Shaw, G
通讯作者：
Shaw, G