Agnieszka Robaszkiewicz

• Dr hab.
• Professor (Associate) at University of Łódź

Some cancer types including bladder, cervical, and uterine cancers are characterized by frequent mutations in EP300 that encode histone acetyltransferase p300. This enzyme can act both as a tumor suppressor and oncogene. In this review, we describe the role of p300 in cancer initiation and progression regarding EP300 aberrations that have been iden...

In addition to innate and gained resistance poliploidy of cancer cells is described as a mechanism responsible for lack of response or cancer relapses after initial patient recovery. Formation of these cells is induced by cyto- and genotoxic agents, which trigger endoreduplication, cytokinesis failure, cell fusion or canibalism. These processes lea...

Variations in several nuclear genes predisposing humans to the development of MODY diabetes have been very well characterized by modern genetic diagnostics. However, recent reports indicate that variants in the mtDNA genome may also be associated with the diabetic phenotype. As relatively little research has addressed the entire mitochondrial genom...

Background/aims: Cancer cell multidrug resistance induced by paclitaxel contributes to the high failure rates of chemotherapy and relapse of the disease. Several mechanisms have been described that underlie the observed resistance, including the overexpression of ABCB1 (P-glycoprotein), which represents an ATP-binding cassette (ABC) transmembrane...

Although cisplatin-based therapies are common among anticancer approaches, they are often associated with the development of cancer drug resistance. This phenomenon is, among others, caused by the overexpression of ATP-binding cassette, membrane-anchored transporters (ABC proteins), which utilize ATP to remove, e.g., chemotherapeutics from intracel...

The increased level of hydrogen peroxide accompanies some modes of macrophage specification and is linked to ROS-based antimicrobial activity of these phagocytes. In this study, we show that activation of toll-like receptors with bacterial components such as LPS is accompanied by the decline in transcription of hydrogen peroxide decomposing enzyme-...

The high expression of some ATP-binding cassette (ABC) transporters is linked to multidrug resistance in cancer cells. We aimed to determine if I-CBP112, which is a CBP/p300 bromodomain inhibitor, altered the vulnerability of the MDA-MB-231 cell line to chemotherapy drugs, which are used in neoadjuvant therapy in patients with triple negative breas...

Under the influence of many factors, such as cytokines or chemokines, macrophages specialize into two subpopulations: pro-inflammatory M1 (classical pathway) or anti-inflammatory M2 macrophages (alternative pathway). Upon stimulation with the bacterial ligand PAM3CSK4 and upon stimulation with LPS (Lipopolysaccharide), TLR (toll-like receptors) 1/2...

Secondary infections cause sepsis that lead to patient disability or death. Contact of macrophages with bacterial components (such as lipopolysaccharide—LPS) activates the intracellular signaling pathway downstream of Toll-like receptors (TLR), which initiate an immune proinflammatory response. However, the expression of nuclear factor-kappa B (NF-...

The conserved Blm10/PA200 proteins are proteasome activators. Previously, we identified PA200-enriched regions in the genome of SH-SY5Y neuroblastoma cells by chromatin immunoprecipitation (ChIP) and ChIP-seq analysis. We also found that selective mitochondrial inhibitors induced PA200 redistribution in the genome. Collectively, our data indicated...

Modulation of PARP1 expression, changes in its enzymatic activity, post-translational modifications, and inflammasome-dependent cleavage play an important role in the development of monocytes and numerous subtypes of highly specialized macrophages. Transcription of PARP1 is governed by the proliferation status of cells at each step of their develop...

The conserved Blm10/PA200 activators bind to the proteasome core and facilitate peptide and protein turnover. Blm10/PA200 proteins enhance proteasome peptidase activity and accelerate the degradation of unstructured proteasome substrates. Our knowledge about the exact role of PA200 in diseased cells, however, is still limited. Here, we show that st...

ATP-zależne kompleksy remodelujące chromatynę stanowią ważny element epigenetycznego mechanizmu regulującego transkrypcję. Posiadają one zdolność do wstawiania, usuwania i przesuwania nukleosomów w obrębie elementów regulatorowych genów kontrolując w ten sposób dostępność DNA dla maszynerii transkrypcyjnej. Jednym z czterech zidentyfikowanych i opi...

Cancer malignancy is usually characterized by unlimited self-renewal. In some types of advanced tumors that are rapidly dividing, gene expression profiles depict elevations in pro-proliferative genes accompanied by coordinately elevated transcription of factors responsible for removal of DNA lesions. In our studies, fast proliferating breast cancer...

The beginning of the early Middle Ages period in Poland (10th-14th century) has been widely debated in the context of an active demographic inflow from other countries and its contribution to the creation of the new country. Finding chamber graves which are considered typical for the Scandinavian ethnic group in a few cemeteries in Poland has becom...

BRG1, an active subunit of the SWI/SNF chromatin-remodeling complex, enables the EP300-dependent transcription of proliferation and DNA repair genes from their E2F/CpG-driven promoters in breast cancer cells. In the current study, we show that BRG1–EP300 complexes are accompanied by poly-ADP-ribose polymerase 1 (PARP1), which emerges as the functio...

The function of macrophages makes them vulnerable to several sources of stress and damage, and thus there is a considerable requirement for some form of resilient molecular defence. Differentiation of human macrophages and their further pro-inflammatory (M1) polarization with bacterial endotoxin is associated with increased transcription of PARP1 a...

Wound healing is a complex multiphase process which can be hampered by many factors including impaired local circulation, hypoxia, infection, malnutrition, immunosuppression, and metabolic dysregulation in diabetes. Redox dysregulation is a common feature of many skin diseases demonstrated by virtually all cell types in the skin with overproduction...

Differentiation of human macrophages predisposes these cells to numerous tasks, i.e. killing invading pathogens, and this entails the need for enhanced intracellular defences against stress, including conditions that may increase DNA damage. Our study shows that expression of DNA repair enzymes, such as PARP1, BRCA1 and XRCC1, are activated during...

In inflamed tissues or during ischemia-reperfusion episodes, activated macrophages produce large amounts of reactive species and are, thus, exposed to the damaging effects of reactive species. Here, our goal was to investigate the mechanism whereby activated macrophages protect themselves from oxidant stress-induced cell death. Hydrogen peroxide-tr...

Although electrophiles are considered as detrimental to cells, accumulating recent evidence indicates that proliferating non-cancerous and particularly cancerous cells utilize these agents for pro-survival and cell cycle promoting signaling. Hence, the redox shift to mild oxidant release must be balanced by multiple defense mechanisms. Our latest f...

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Bone morphogenetic protein-2 (BMP-2), is a potential factor to enhance osseointegration of dental implants. However, the appropriate cellular system to investigate the osteogenic effect of BMP-2 in vitro in a standardized manner still needs to be defined. The aim of this study was to examine the effect of BMP-2 on the cell proliferation and osteoge...

Apart from protecting genome PARP1 has been documented to regulate many intracellular processes inter alia gene transcription by physically interacting with chromatin bound proteins and by their ADP-ribosylation. Our recent findings indicate that expression of PARP1 decreases during the differentiation of human CD34+ hematopoietic stem cells to mon...

Redox regulation has been proposed to control various aspects of carcinogenesis, cancer cell growth, metabolism, migration, invasion, metastasis and cancer vascularization. As cancer has many faces, the role of redox control in different cancers and in the numerous cancer-related processes often point in different directions. In this review, we foc...

Differentiation of certain cell types is followed by a downregulation of PARP1 expression. We show that the reduction in the abundance of PARP1 in hematopoietic progenitor cells and monocytes is tightly controlled by the cell cycle. The differentiation-associated cell cycle exit induces E2F1 replacement with E2F4 at the PARP1 promoter and the assem...

Differentiation of human monocytes is associated with proliferation arrest resulting from activation of the inter alia retinoblastoma protein family of gene repressors, which target gene promoters in an E2F-dependent manner. To investigate RBL2 contribution to defining monocyte phenotype and function, we used primer libraries. We identified genes e...

Hallmarks of cancer cells include uncontrolled growth and rapid proliferation; thus, cyclin-dependent kinases are a therapeutic target for cancer treatment. Treating non-small lung cancer cells with sublethal concentrations of the CDK4/6 inhibitors, ribociclib (LEE011) and palbociclib (PD0332991), which are approved by the FDA for anticancer therap...

Inhibitors of CDK4/6 – LEE011 and PD0332991 have been tested in clinical trials in combination with other anticancer drugs for their use in cancer treatment. These compounds are documented to arrest cell cycle progression. We show that in human lung cancer cells these agents cause cell accumulation in G1 phase and repression of PARP1 transcription...

Inhibitors of CDK4/6 – LEE011 and PD0332991 have been tested in clinical trials in combination with other anticancer drugs for their use in cancer treatment. These compounds are documented to arrest cell cycle progression. We show that in human lung cancer cells these agents cause cell accumulation in G1 phase and repression of PARP1 transcription...

Contrary to common perception bone is a dynamic organ flexibly adapting to changes in mechanical loading by shifting the delicate balance between bone formation and bone resorption carried out by osteoblasts and osteoclasts, respectively. In the past decades numerous studies demonstrating production of reactive oxygen or nitrogen intermediates, eff...

The homeostasis of the bone and the proper bone remodelling is provided by the balance in the number and activity of bone formimg osteoblast and bone resorbing osteoclasts. Although these cells originate from distinct precursors (mesenchymal and hemopoidal stem cells, respectively) their differentiation is accompanied by PARP1 activation and ADP-ri...

While ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) and its enzymatic activity have been shown to be important for reprogramming and differentiation of cells, such as during adipogenesis, their role and mechanism in regulating osteoclastogenesis and bone homeostasis are largely unknown. Here, in cell culture-based RANKL-ind...

Contemporary historical anthropology and classical archaeology are concerned not only with such fundamental issues as the origins of ancient human populations and migration routes, but also with the formation and development of interpopulation relations and the mixing of gene pools as a result of interbreeding between individuals representing diffe...

Contrary to common perception bone is a dynamic organ flexibly adapting to changes in mechanical loading by shifting the delicate balance between bone formation and bone resorption carried out by osteoblasts and osteoclasts, respectively. In the past decades numerous studies demonstrating production of reactive oxygen or nitrogen intermediates, eff...

Osteogenic differentiation is a multistep process regulated by a diverse set of morphogenic and transcription factors. Previously we identified endogenous hydrogen peroxide-induced poly(ADP-ribose) polymerase-1 (PARP1) activation as mediator of osteodifferentiation and associated cell death. Here we set out to investigate whether or not activation...

Electrophilic attack of hypochlorous acid on unsaturated bonds of fatty acyl chains is known to result mostly in chlorinated products that show cytotoxicity to some cell lines and were found in biological systems exposed to HOCl. This study aimed to investigate more deeply the products and the mechanism underlying cytotoxicity of phospholipid-HOCl...

Poly(ADP-ribosyl)ation (PARylation) is a reversible protein modification carried out by the concerted actions of poly(ADP-ribose) polymerase (PARP) enzymes and poly(ADP-ribose) (PAR) decomposing enzymes such as PAR glycohydrolase (PARG) and ADP-ribosyl hydrolase 3 (ARH3). Reversible PARylation is a pleiotropic regulator of various cellular function...

We set out to investigate the role of poly(ADP-ribosylation), the attachment of NAD(+)-derived (ADP-ribose)(n) polymers to proteins, in the regulation of osteogenic differentiation of SAOS-2 cells and mesenchymal stem cells. In osteogenic differentiation medium, SAOS-2 cells showed mineralization and expressed alkaline phosphatase and osteoblastic...

Hypochlorite is a strong oxidant, generated under pathological conditions, with the potency to introduce chlorine atom into a number of molecules. 3-Chloro- and 3,5-dichlorotyrosine are documented to be generated by this oxidant and their elevated levels were found in many diseases. Thus, we decided to check the possibility of use of FITC-conjugate...

Generation of chloric acid(I) and reactive oxygen and nitrogen species by activated phagocytes is associated with the course of many inflammatory-related lung diseases. Thus, we studied the effects of HOCl on the redox state of A549 cells as well as on the activity of enzymes involved in cell protection against oxidants. Additionally, we determined...

Hypochlorite generated in vivo under pathological conditions is a known oxidant and chlorinating agent, able to react with proteins and lipids, which affects the stability of biological membranes. Reaction with unsaturated fatty acyl chains in glycerophospholipids such as phosphatidylcholine results in the formation of chlorohydrins. The aim of thi...

Peroxynitrite and hypochlorite are oxidants relevant in many pathological situations. We propose a simple spectrofluorometric assay to determine antioxidant capacity against hypochlorite and peroxynitrite based on protection against fluorescein bleaching. The assay can be performed on a microplate and requires minute amounts of material. Standard a...

Hypochlorous acid, a chlorinating and oxidative agent, has been reported to be implicated in many pathologies. Its markers were found under inflammatory conditions and, at least some of it reveals biological activity. Thus, in this paper we examined whether N-chloroamino acids may act as mediators of the action of hypochlorous acid in cell culture....

According to mitochondrial theory of ageing the ageing process results from accumulation of mitochondrial DNA (mtDNA) damage. Close vicinity of mtDNA molecule to the source of reactive oxygen species, electron transport chain, potentiates degradation of nucleic acid chemical components. The most common types of mtDNA damage generated are point muta...

Reactive oxygen and nitrogen species are attributed to initiation and propagation of many diseases. The demonstration of elevated activity of myeloperoxidase and the level of 3-chlorotyrosine in atherosclerosis, kidney diseases and chronic inflammations brought about the interest in the biological role of another strong oxidant--hypochlorite. Conce...

One of the nutritional benefits of mushrooms is the presence of bioactive secondary metabolites which have been reported to exert various beneficial effects in vivo. Therefore, we selected thirteen frequently consumed species of Polish mushrooms and determined the concentration of polyphenols, flavonoids, β-carotene, and lycopene in aqueous and met...

Peroxynitrite and hypochlorite are oxidants relevant in many pathological situations. We propose a simple spectrophotometric assay to determine antioxidant capacity against hypochlorite and peroxynitrite based on protection against Pyrogallol Red decolorization. The assay can be performed on a microplate and requires minute amounts of material. Sta...

The increase in the amount of oxidatively modified proteins is a hallmark of ageing and age-related disorders. This paper is aimed at a verification of the hypothesis that N-chloroamino acids, products of reaction between hypochlorite generated in vivo under pathological conditions and free amino acids, may induce oxidative modifications of erythro...

Amino acids present in blood plasma may be targets for oxidation and chlorination by HOCl/OCl(-). N-Chloroamino acids have been reported to be less reactive, but more selective than HOCl/OCl(-) in their reactions; therefore, they may act as secondary mediators of HOCl/OCl(-)-induced injury. This study compared the effects of five N-chloroamino acid...

Quercetin, a common plant polyphenol, has been reported to show both antioxidant and prooxidant properties. We studied the effects of quercetin on A549 cells in in vitro culture. We found that low concentrations of the flavonoid stimulated cell proliferation and increased total antioxidant capacity (TAC) of the cells; while higher concentrations of...