Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat
It has been demonstrated that nucleoporins such as RanGap1 and Nup205 showed intense nuclear localization and aberrant nuclear aggregates, and they were colocalized in C9orf72ALS cases; the disrupted NCT at the NPC may lead to the dysfunction of cells and is a fundamental mechanism for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (Zhang et al., 2015).
Subcellular localization of such proteins may change in response to various sources of stress (Suntharalingam and Wente, 2003; Chu et al., 2007). The dysfunctional NCT system has been demonstrated to be involved in the pathogenesis of neurodegenerative diseases such as ALS, FTD, and Alzheimer disease (AD) (Sheffield et al., 2006; Kinoshita et al., 2009; Zhang et al., 2015), which has also been reported to be associated with heart disease (Zhang et al., 2008; Cortes et al., 2010; Tarazón et al., 2012), neoplasms, and many other disorders (Cronshaw and Matunis, 2004). However, there has been no investigations on the changes of NPC proteins in cerebral ischemia. Furthermore, emerging evidence has demonstrated that oxidative stress could significantly damage NCT and affect nucleocytoplasmic trafficking (Kodiha et al., 2008; Crampton et al., 2009; Kotwaliwale and Dernburg, 2009). Oxidative stress is also known to participate in the pathophysiology of cerebral ischemia (Hayashi et al., 1999). The NPCs play an important role in coordinating the critical steps of the selective bidirectional transport across the nuclear pore (Suntharalingam and Wente, 2003; Chu et al., 2007); therefore, in the present study, we investigated the temporal alterations of nucleoporins and their interactions in ischemic rat brains.