Renal dysfunction markers in patients with diabetes mellitus type 1 after kidney or simultaneous kidney-pancreas transplantation

Abstract

ТЕЗИСЫ ДОКЛАДОВ 4-Й КОНФЕРЕНЦИИ ЕВРОПЕЙСКОЙ АССОЦИАЦИИ МОЛОДЫХ ЭНДОКРИНОЛОГОВacids in blood was considered as one of the main causes of type 2 diabetes mellitus development. Although precise molecular mechanisms of this process are still unclear, there are some indications that the p38 MAPK signaling pathway could be involved.Aim, material and methods. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in human pancreatic β-cells NES2Y. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested.Results. We have found that saturated SA at apoptosis-inducing concentration (1 mM) activated the p38 MAPK signaling pathway MKK3/6→p38 MAPK→MAPKAPK-2 and inhibited the ERK signaling pathway c-Raf→MEK1/2→ERK1/2. The inhibition of p38 MAPK expression by siRNA silencing had no signifi cant eff ect on cell viability or the level of phosphorylated ERK pathway members after SA administration. The inhibition of p38 MAPK activity by the specifi c inhibitor SB202190 resulted in noticeable activation of ERK pathway members after SA treatment but in no signifi cant eff ect on cell viability. p38 MAPK overexpression by plasmid transfection produced no signifi cant infl uence on cell viability or ERK pathway activation after SA exposure. The activation of p38 MAPK by the specifi c activator anisomycin led to apoptosis induction similar to application of SA (PARP cleavage and caspase-7, -8, and -9 activation) and in inhibition of ERK pathway members.Conclusions. We demonstrated that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway and that this activation could be involved in apoptosis induction by SA in the human pancreatic β-cells NES2Y. However, this involvement does not seem to play a key role. Crosstalk between p38 MAPK pathway activation and ERK pathway inhibition in NES2Y cells seems likely. Thus, the ERK pathway inhibition by p38 MAPK activation does not also seem to be essential for SAinduced apoptosis. KEYWORDS p38 MAPK; ERK; fatty acids; pancreatic beta-cells; apoptosis; NES2Y. Введение. Снижение функциональной активности и апоптоза β-клеток поджелудочной железы в ответ на стойкое повышение концентрации насыщенных жирных кислот в крови ранее рассматривалось в качестве одной из основных причин развития сахарного диабета 2-го типа. Хотя точные молекулярные механизмы этого процесса до сих пор не известны, есть данные о важной роли каскада р38 МАРК. FOUNDING INFOЦель, материал и методы. В нашем исследовании была проведена оценка роли р38 МАРК каскадного пути в ак-тивации апоптоза SA β-клеток поджелудочной железы че-ловека NES2Y. Также изучена взаимосвязь между актива-цией каскада р38 МАРК и ингибированием пути ERK по-сле нанесения SA.Результаты. Нами было выявлено, что насыщенные SA при концентрации, индуцирующей апоптоз (1 мМ), активирует р38 МАРК сигнальным каскадом MKK3/6 → р38 МАРК → MAPKAPK-2 и ингибирует ERK сигнальный путь C-Raf → MEK1/2 → ERK1/2. Ингибирование экспрес-сии МАРК р...