Activation of AMP-activated protein kinase by metformin induces protein acetylation in prostate and ovarian cancer cells

AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of metabolism. AMPK functions as a fuel gauge monitoring systemic and cellular energy status. Activation of AMPK occurs when the intracellular AMP/ATP ratio increases and leads to a metabolic switch from anabolism to catabolism. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in de novo synthesis of fatty acids. AMPK thus regulates homeostasis of acetyl-CoA, a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription. Nucleocytosolic concentration of acetyl-CoA affects histone acetylation and links metabolism and chromatin structure. Here we show that activation of AMPK with the widely used antidiabetic drug metformin or with the AMP mimetic 5-aminoimidazole-4-carboxamide ribonucleotide increases the inhibitory phosphorylation of ACC and decreases the conversion of acetyl-CoA to malonyl-CoA, leading to increased protein acetylation and altered gene expression in prostate and ovarian cancer cells. Direct inhibition of ACC with allosteric inhibitor 5-(tetradecyloxy)-2-furoic acid also increases acetylation of histones and non-histone proteins. Because AMPK activation requires liver kinase B1, metformin does not induce protein acetylation in liver kinase B1-deficient cells. Together, our data indicate that AMPK regulates the availability of nucleocytosolic acetyl-CoA for protein acetylation and that AMPK activators, such as metformin, have the capacity to increase protein acetylation and alter patterns of gene expression, further expanding the plethora of metformin's physiological effects

Symbiosis between river and dry lands: phycobiont dynamics on river gravel bars (Supplementary datasets))

Multiple alignments of the ITS rDNA (of Asterochloris and Stereocaulon) and actin type I loci sequences built using MAFFT v7, applying the Q-INS-i strategy

Phycobiont selection along temperature gradient

Lichens are an iconic example of symbiotic systems whose ecology is shaped by the requirements of the symbionts. Previous studies suggest that fungal (mycobionts), as well as photosynthesizing (phycobionts or cyanobionts) partners have a specific range of acceptable symbionts that can be chosen according to specific environmental conditions. This study aimed to investigate the effects of climatic conditions and mycobiont identity on phycobiont distribution within the lichen genera Stereocaulon, Cladonia, and Lepraria. The study area comprised the Canary Islands, Madeira, Sicily, and the Aeolian Islands, spanning a wide range of climatic conditions. These islands are known for their unique and diverse fauna and flora; however, lichen phycobionts have remained unstudied in most of these areas. In total, we genetically analyzed 339 lichen samples. The phycobiont pool differed significantly from that outside the studied area. Asterochloris mediterranea was identified as the most abundant phycobiont. However, its distribution was limited by climatic constraints. Other species of Asterochloris and representatives of the genera Chloroidium, Vulcanochloris, and Myrmecia were also recovered as phycobionts. The selection of symbiotic partners from the local phycobiont pool was driven by mycobiont specificity (i.e., the taxonomic range of acceptable partners) and the environmental conditions, mainly temperature. Interestingly, the dominant fungal species responded differently in their selection of algal symbionts along the environmental gradients. Cladonia rangiformis associated with its phycobiont A. mediterranea in a broader range of temperatures than Stereocaulon azoreum, which favors other Asterochloris species along most of the temperature gradient. S. vesuvianum associated with Chloroidium spp., which also differed in their temperature optima.Data: 7 DNA alignments (ITS rDNA: Asterochloris, Chloroidium, Vulcanochloris, Cladonia, Lepraria, Stereocaulon; actin type I gene: Asterochloris)THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Symbiosis between river and dry lands: phycobiont dynamics on river gravel bars (Supplementary datasets))

Multiple alignments of the ITS rDNA (of Asterochloris and Stereocaulon) and actin type I loci sequences built using MAFFT v7, applying the Q-INS-i strategy

Transcriptional Regulation of Chemokine Expression in Ovarian Cancer

The increased expression of pro-inflammatory and pro-angiogenic chemokines contributes to ovarian cancer progression through the induction of tumor cell proliferation, survival, angiogenesis, and metastasis. The substantial potential of these chemokines to facilitate the progression and metastasis of ovarian cancer underscores the need for their stringent transcriptional regulation. In this Review, we highlight the key mechanisms that regulate the transcription of pro-inflammatory chemokines in ovarian cancer cells, and that have important roles in controlling ovarian cancer progression. We further discuss the potential mechanisms underlying the increased chemokine expression in drug resistance, along with our perspective for future studies

Increased p50/p50 NF-κB Activation in Human Papillomavirus Type 6- or Type 11-Induced Laryngeal Papilloma Tissue

We have observed elevated NF-κB DNA-binding activity in nuclear extracts from human papillomavirus type 6- and 11-infected laryngeal papilloma tissues. The predominant DNA-binding species is the p50/p50 homodimer. The elevated NF-κB activity could be correlated with a reduced level of cytoplasmic IκBβ and could be associated with the overexpression of p21(CIP1/WAF1) in papilloma cells. Increased NF-κB activity and cytoplasmic accumulation of p21(CIP1/WAF1) might counteract death-promoting effects elicited by overexpressed PTEN and reduced activation of Akt and STAT3 previously noted in these tissues

Anti-inflammatory actions of endogenous and exogenous interleukin-10 versus glucocorticoids on macrophage functions of the newly born

OBJECTIVE: To determine whether specific macrophage immune functions of the newly born are insensitive to the actions of therapeutic levels of dexamethasone (DEX), previously measured in infants with bronchopulmonary dysplasia (BPD), compared with betamethasone (BETA) and exogenous or endogenous interleukin-10 (IL-10). STUDY DESIGN: Macrophages were differentiated from cord blood monocytes (N=18). A serial dose-response (around 10(-8)M), in vitro study was used to examine the effect of DEX, BETA and IL-10, on proinflammatory (PI) cytokine release, phagocytosis and respiratory burst. RESULT: Exogenous IL-10 (10(-8)M) significantly (P \u3c 0.05) inhibited the endotoxin-stimulated release of IL-6, IL-8 and tumor necrosis factor by 63 to 82% with no significant effect by DEX and BETA. There was no inhibition by these three agents at 10(-8)M on phagocytosis and respiratory burst. Inhibition of endogenous IL-10 with a monoclonal antibody significantly increased endotoxin-stimulated cytokine release by at least fourfold. CONCLUSION: Macrophages were relatively insensitive to therapeutic levels of DEX and BETA with regard to PI cytokine release. This study provides rationale for translational and preclinical research using airway instillation of IL-10 for the treatment of BPD