Transcriptional and translational regulation of cytokine signaling in inflammatory β-cell dysfunction and apoptosis.
Disease is conventionally viewed as the chaotic inappropriate outcome of deranged tissue function resulting from aberrancies in cellular processes. Yet the patho-biology of cellular dysfunction and death encompasses a coordinated network no less sophisticated and regulated than maintenance of homeostatic balance. Cellular demise is far from passive subordination to stress but requires controlled coordination of energy-requiring activities including gene transcription and protein translation that determine the graded transition between defensive mechanisms, cell cycle regulation, dedifferentiation and ultimately to the activation of death programmes. In fact, most stressors stimulate both homeostasis and regeneration on one hand and impairment and destruction on the other, depending on the ambient circumstances. Here we illustrate this bimodal ambiguity in cell response by reviewing recent progress in our understanding of how the pancreatic β cell copes with inflammatory stress by changing gene transcription and protein translation by the differential and interconnected action of reactive oxygen and nitric oxide species, microRNAs and posttranslational protein modifications.
Section of Endocrinological Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Guy W
GW
Novotny
Morten
M
Lundh
Marie B
MB
Backe
Dan P
DP
Christensen
Jakob B
JB
Hansen
Mattias S
MS
Dahllöf
Emil M H
EM
Pallesen
Thomas
T
Mandrup-Poulsen
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000235:genetics* / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000473:pathology* / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
D016207:Cytokines; D018836:Inflammation Mediators; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D006655:Histone Deacetylases