24 research outputs found
Impaired mitochondrial biogenesis contributes to depletion of functional mitochondria in chronic MPP+ toxicity: dual roles for ERK1/2
The regulation of mitochondrial quality has emerged as a central issue in neurodegeneration, diabetes, and cancer. We utilized repeated low-dose applications of the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) over 2 weeks to study cellular responses to chronic mitochondrial stress. Chronic MPP+ triggered depletion of functional mitochondria resulting in diminished capacities for aerobic respiration. Inhibiting autophagy/mitophagy only partially restored mitochondrial content. In contrast, inhibiting activation of extracellular signal-regulated protein kinases conferred complete cytoprotection with full restoration of mitochondrial functional and morphological parameters, enhancing spare respiratory capacity in MPP+ co-treated cells above that of control cells. Reversal of mitochondrial injury occurred when U0126 was added 1 week after MPP+, implicating enhanced repair mechanisms. Chronic MPP+ caused a >90% decrease in complex I subunits, along with decreases in complex III and IV subunits. Decreases in respiratory complex subunits were reversed by co-treatment with U0126, ERK1/2 RNAi or transfection of dominant-negative MEK1, but only partially restored by degradation inhibitors. Chronic MPP+ also suppressed the de novo synthesis of mitochondrial DNA-encoded proteins, accompanied by decreased expression of the mitochondrial transcription factor TFAM. U0126 completely reversed each of these deficits in mitochondrial translation and protein expression. These data indicate a key, limiting role for mitochondrial biogenesis in determining the outcome of injuries associated with elevated mitophagy
A retrospective analysis of risk factors of oromaxillofacial infection in patients presenting to a hospital emergency ward
High Blood Pressure and Its Association with Body Weight among Children and Adolescents in the United Arab Emirates
Attenuation of diet-induced hypothalamic inflammation following bariatric surgery in female mice
Reconstruction of historical lead contamination and sources in Lake Hailing, Eastern China: a Pb isotope study
P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation
P90 RSK, but not Akt/PKB, facilitates nuclear retention of Chk1 through Chk1–Ser-280 phosphorylation in response to serum stimulation. Chk1–Ser-280 phosphorylation is also elevated in a p90 RSK–dependent manner after UV irradiation and accelerates the Chk1 activation process (Ser-345 and Ser-296 phosphorylation on Chk1) after UV irradiation