NF‐κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress

Abstract

Brain cells display an amazing ability to respond to several different types of environmental stimuli and integrate this response physiologically. Some of these responses can outlive the original stimulus by days, weeks or even longer. Long-lasting changes in both physiological and pathological conditions occurring in response to external stimuli are almost always mediated by changes in gene expression. To effect these changes, cells have developed an impressive repertoire of signaling systems designed to modulate the activity of numerous transcription factors and epigenetic mechanisms affecting the chromatin structure. Since its initial characterization in the nervous system, NF-κB has shown to respond to multiple signals and elicit pleiotropic activities suggesting that it may play a pivotal role in integration of different types of information within the brain. Ample evidence demonstrates that NF-κB factors are engaged in and necessary for neuronal development and synaptic plasticity, but they also regulate brain response to environmental noxae. By focusing on the complexity of NF-κB transcriptional activity in neuronal cell death, it emerged that the composition of NF-κB active dimers finely tunes the neuronal vulnerability to brain ischemia. Even though we are only beginning to understand the contribution of distinct NF-κB family members to the regulation of gene transcription in the brain, an additional level of regulation of NF-κB activity has emerged as operated by the epigenetic mechanisms modulating histone acetylation. We will discuss NF-κB and epigenetic mechanisms as

Más allá de las moléculas...lo que los clínicos desconocen: Acortando brechas

“…De igual manera, existen estudios que relacionan las modificaciones epigenéticas con dolor (112,126). La regulación de la expresión génica a través de la epigenética cumple un papel importante en la plasticidad neuronal y en la respuesta celular a los cambios ambientales (127). Existen reportes que asocian la epigenética con la transición del dolor agudo a crónico después de una lesión (112), y dolor y analgesia (126).…”

Systems approach to the study of brain damage in the very preterm newborn

“…Nevertheless the authors of one paper felt compelled to write, “One of the greatest challenges in studying Notch signaling is the inability to predict the outcome of Notch activation, owing to its multiple roles” (Ables et al, 2011 ), while others wrote, “Although, this pathway is remarkably short, with no second messenger involved, it regulates expression of more than hundred target genes in a tissue-specific manner” (Borggrefe and Liefke, 2012 ). In addition to the contribution of context and cross-talk, some of the multiplicity and diversity of the pleiotropic functions of transcription factors have been attributed to epigenetic tendencies (Sarnico et al, 2012 ).…”

“…We provide just a hint of the complexity of these three pathways and their interconnections in the Figure 1 . Not shown in the Figure 1 are the relationships between adult brain diseases and NF-κB (Cai, 2009 ; Ridder and Schwaninger, 2009 ; Harari and Liao, 2010 ; Nogueira et al, 2011 ; Nestler, 2012 ; Sako et al, 2012 ; Crampton and O’keeffe, 2013 ; Hoesel and Schmid, 2013 ; Mc Guire et al, 2013 ; Zhou and Hu, 2013 ; Alvira, 2014 ; Gupta and Sharma, 2014 ; Laprairie et al, 2014 ; Snow et al, 2014 ; Tu et al, 2014 ; Uekawa et al, 2014 ; Xiao et al, 2014 ; Zhou and Zhou, 2014 ; Zhao et al, 2015 ), NRF2 (van Muiswinkel and Kuiperij, 2005 ; Kumar et al, 2012 ; Sandberg et al, 2013 ; Arnold et al, 2014 ; Ding et al, 2014 ; Chen et al, 2015b ; Djordjevic et al, 2015 ; Zhao et al, 2015 ), and Notch (John et al, 2002 ; Minter et al, 2005 ; Arumugam et al, 2006 ; Ban et al, 2006 ; Nagarsheth et al, 2006 ; Elyaman et al, 2007 ; Jurynczyk et al, 2008 ; Yuan and Yu, 2010 ; Tsugane et al, 2012 ), as well as between epigenetic phenomena and NF-κB (Arzate-Mejía et al, 2011 ; Sarnico et al, 2012 ; Narayan et al, 2015 ), NRF2 (Martinez et al, 2009 ; Arzate-Mejía et al, 2011 ; Gao et al, 2015 ), and Notch (Arzate-Mejía et al, 2011 ; Cama et al, 2013 ; Sun et al, 2014 ; Schwanbeck, 2015 ).…”

“…To add to the complexity, epigenetic phenomena influence the balance between inflammatory and anti-inflammatory capabilities (Correa et al, 2011 ; Sarnico et al, 2012 ; Aithal and Rajeswari, 2013 ; Cai et al, 2013 ; Su et al, 2013 ). As might be expected, systems biologists are paying attention to epigenetic phenomena (Sookoian et al, 2013 ; Dekker, 2014 ; Maze et al, 2014 ; Schadt et al, 2014 ; Klin et al, 2015 ; Thakur et al, 2015 ).…”

Pattern of neuronal expression of transcription factors NF-kappaB under different modes of hypobaric hypoxia

“…Однако, очевидно, процессы регуляции активности NF-kB гораздо сложнее. В последнее время предполагается, что помимо классического пути активации NF-kB и отделения за счет фосфорилирования ингибирующей субъединицы IкB [17], существует ряд эпигенетических механизмов регуляции активности NF-kB [33]. Этот фактор может подвергаться пострансляционным модификациям: метили-рованию, ацетилированию и фосфорилированию [13].…”