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Article ; Online: A brief overview of BNIP3L/NIX receptor‐mediated mitophagy

Mija Marinković / Ivana Novak

FEBS Open Bio, Vol 11, Iss 12, Pp 3230-

2021 Volume 3236

Abstract: Mitophagy is a form of autophagy specialized to selectively remove mitochondria. Although the PINK1/Parkin pathway is the best described mitophagy of damaged mitochondria, receptor/mediated mitophagy seems to have a pivotal role in cellular development ... ...

Abstract	Mitophagy is a form of autophagy specialized to selectively remove mitochondria. Although the PINK1/Parkin pathway is the best described mitophagy of damaged mitochondria, receptor/mediated mitophagy seems to have a pivotal role in cellular development and specialization. The most studied mitophagy receptor BCL2/adenovirus E1B 19‐kDa‐interacting protein 3‐like (BNIP3L/NIX) is shown to be important for the programmed removal of healthy mitochondria during terminal differentiation of erythrocytes, but its role has been proven in various cell types. Despite recent advances in our understanding of its regulation by phosphorylation and dimerization, there remain numerous questions on how BNIP3L/NIX tightly balances between cellular life and death decisions. This brief review intends to summarize ongoing dilemmas related to BNIP3L/NIX.
Keywords	BNIP3L/NIX ; mitochondria ; mitophagy ; reticulocytes ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acid-base transport in pancreas – new challenges

IvanaNovak

Frontiers in Physiology, Vol

2013 Volume 4

Abstract: Along the gastrointestinal tract a number of epithelia contribute with acid or basic secretions in order to aid digestive processes. The stomach and pancreas are the most extreme examples of acid (H+) and base (HCO3-) transporters, respectively. ... ...

Abstract	Along the gastrointestinal tract a number of epithelia contribute with acid or basic secretions in order to aid digestive processes. The stomach and pancreas are the most extreme examples of acid (H+) and base (HCO3-) transporters, respectively. Nevertheless, they share the same challenges of transporting acid and bases across epithelia and effectively regulating their intracellular pH. In this review, we will make use of comparative physiology to enlighten the cellular mechanisms of pancreatic HCO3- and fluid secretion, which is still challenging physiologists. Some of the novel transporters to consider in pancreas are the proton pumps (H+-K+-ATPases), as well as the calcium-activated K+ and Cl- channels, such as KCa3.1 and TMEM16A/ANO1. Local regulators, such as purinergic signalling, fine-tune and coordinate pancreatic secretion. Lastly, we speculate whether dys-regulation of acid-base transport contributes to pancreatic diseases including cystic fibrosis, pancreatitis and cancer.
Keywords	proton transport ; pancreatic duct ; ik ; Bicarbonate transport ; KCa3.1 ; H+-K+-ATPase ; TMEM16A ; ANO1 ; Physiology ; QP1-981 ; Science ; Q
Subject code	500
Language	English
Publishing date	2013-12-01T00:00:00Z
Publisher	Frontiers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cell volume regulation in epithelial physiology and cancer

IvanaNovak

Frontiers in Physiology, Vol

2013 Volume 4

Abstract: The physiological function of epithelia is transport of ions, nutrients and fluid either in secretory or absorptive direction. All of these processes are closely related to cell volume changes, which are thus an integrated part of epithelial function. ... ...

Abstract	The physiological function of epithelia is transport of ions, nutrients and fluid either in secretory or absorptive direction. All of these processes are closely related to cell volume changes, which are thus an integrated part of epithelial function. Transepithelial transport and cell volume regulation both rely on the spatially and temporally coordinated function of ion channels and transporters. In healthy epithelia, specific ion channels/transporters localize to the luminal and basolateral membranes, contributing to functional epithelial polarity. In pathophysiological processes such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed.
Keywords	Drug Resistance ; Ion Transport ; breast cancer ; Pancreatic Cancer ; Epithelia ; K+ channels ; secretion ; Stroma ; tumour microenvironment ; Cl- channels ; Physiology ; QP1-981 ; Science ; Q
Subject code	571
Language	English
Publishing date	2013-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

Ivana Novak / Haoran Yu / Lara Magni / Ganga Deshar

International Journal of Molecular Sciences, Vol 21, Iss 8781, p

2020 Volume 8781

Abstract: The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of ... ...

Abstract	The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of purinergic and adenosine receptors, as well as ecto-nucleotidases regulate normal pancreatic cells and various cells within the pancreatic tumor microenvironment. In particular, we focus on the P2X7 receptor, P2Y 2 and P2Y 12 receptors, as well as A 2 receptors and ecto-nucleotidases CD39 and CD73. Recent studies indicate that targeting one or more of these candidates could present new therapeutic approaches to treat pancreatic cancer. In pancreatic cancer, as much as possible of normal pancreatic function should be preserved, and therefore physiology of purinergic signaling in pancreas needs to be considered.
Keywords	pancreatic cancer ; PDAC ; pancreatic stellate cells ; PSC ; fibrosis ; immune cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Resveratrol as antioxidant in cardiac surgery: is there potential for clinical application?

Planinc, Mislav / Jovanović, Ivana Novak / Rašić, Dubravka / Peraica, Maja / Sutlić, Željko

Arhiv za higijenu rada i toksikologiju

2022 Volume 73, Issue 4, Page(s) 256–259

Abstract: Cardiopulmonary bypass (CPB) is an essential technique in cardiac surgery but is also associated with adverse effects, including the systemic inflammatory response syndrome that manifests itself as ischaemia-reperfusion injury and multi-organ dysfunction. ...

Abstract	Cardiopulmonary bypass (CPB) is an essential technique in cardiac surgery but is also associated with adverse effects, including the systemic inflammatory response syndrome that manifests itself as ischaemia-reperfusion injury and multi-organ dysfunction. The aim of this mini review is to take a look at the current knowledge of resveratrol, a stilbenoid and natural antioxidant believed to have many cardioprotective effects including vasodilation, lowering of blood pressure and reactive oxygen species levels, suppression of low-density lipoprotein peroxidation, and mitigation of ischaemia/-reperfusion injury. We mostly focus on its cardioprotective potential in patients undergoing cardiac surgery supported by CPB. Current findings, however, are still inconclusive and call for further research, including clinical trials.
MeSH term(s)	Humans ; Antioxidants/therapeutic use ; Resveratrol/therapeutic use ; Cardiac Surgical Procedures/adverse effects ; Cardiopulmonary Bypass/adverse effects ; Cardiopulmonary Bypass/methods ; Reactive Oxygen Species
Chemical Substances	Antioxidants ; Resveratrol (Q369O8926L) ; Reactive Oxygen Species
Language	English
Publishing date	2022-12-30
Publishing country	Croatia
Document type	Review ; Journal Article
ZDB-ID	127289-5
ISSN	1848-6312 ; 0004-1254
ISSN (online)	1848-6312
ISSN	0004-1254
DOI	10.2478/aiht-2022-73-3643
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Article ; Online: A new, simplified model for the estimation of polyphenol oxidation potentials based on the number of OH groups.

Jovanović, Ivana Novak / Miličević, Ante

Arhiv za higijenu rada i toksikologiju

2017 Volume 68, Issue 2, Page(s) 93–98

Abstract: We present a new and simpler regression model for the estimation of the first oxidation potentials (Ep1) of flavonoids based on the number of phenolic, alcoholic, and carboxylic OH groups. In the regression we included the Ep1 of 12 polyphenols (mostly ... ...

Abstract	We present a new and simpler regression model for the estimation of the first oxidation potentials (Ep1) of flavonoids based on the number of phenolic, alcoholic, and carboxylic OH groups. In the regression we included the Ep1 of 12 polyphenols (mostly flavonols and catechins) that were measured in our laboratory at pH 3. The model yielded r=0.986 and SE=0.040. Later successive inclusions of previously reported Ep values into the regression model, 7 at pH 3, the model (N=19) yielded r=0.980, SE=0.046 and 19 at pH 7 the model (N=38), yielded r=0.985, SE=0.044.
Language	English
Publishing date	2017-06-27
Publishing country	Croatia
Document type	Journal Article
ZDB-ID	127289-5
ISSN	1848-6312 ; 0004-1254
ISSN (online)	1848-6312
ISSN	0004-1254
DOI	10.1515/aiht-2017-68-2988
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mediterranean Diet Adherence and Nutritional Status in Dalmatian Diabetic Hypertensive Patients Regarding Presence of Chronic Kidney Disease—Is There Any Difference?

Dora Bučan Nenadić / Josipa Radić / Ela Kolak / Marijana Vučković / Ivana Novak / Marija Selak / Mislav Radić

International Journal of Environmental Research and Public Health, Vol 19, Iss 2293, p

2022 Volume 2293

Abstract: In recent years, the Mediterranean diet has emerged as one of the dietary patterns that could have positive effects on overall health as well in the treatment of non-communicable chronic diseases. The aim of this cross-sectional study was to determine ... ...

Abstract	In recent years, the Mediterranean diet has emerged as one of the dietary patterns that could have positive effects on overall health as well in the treatment of non-communicable chronic diseases. The aim of this cross-sectional study was to determine differences in adherence to the Mediterranean diet (MeDi) and nutritional status in patients with type 2 diabetes mellitus (T2DM) and arterial hypertension (AH) regarding the presence of chronic kidney disease (CKD). Two hundred and forty-eight Dalmatian diabetic hypertensive patients (DDHP) were included, and 164 (66.1%) of them had CKD. Data about anthropometric parameters, clinical and laboratory parameters, as well as lifestyle questionnaire and Mediterranean Diet Serving Score (MDSS) were collected for each study participant. Furthermore, body composition was assessed using MC-780 Multi Frequency Segmental Body Mass Analyzer (Tanita). Body mass index (BMI) as well as waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were calculated. Results showed that only 8.9% of DDHP were adherent to the MeDi without significant differences regarding the presence of CKD. Therefore, only 9.1% of participants with CKD were adherent to the MeDi. Dietary recommendations were received by 52.8% of DDHP and 49.4% with CKD, while only 12.8% of those with CKD were adherent to the given recommendations. The results showed that 88.3% of DDHP and 87.8% of the DDHP with CKD were overweight or obese. Statically significant lower frequency of nut intake suggested by the MeDi was found in those participants with CKD ( p = 0.02). Therefore, the significant associations between adherence to each MeDi component as well as MDSS score with the development of CKD among all study subjects were not found. In conclusion, the results showed a low level of nutritional care in our region and low adherence to MeDi among DDHP. According to the results, there is an urgent need to improve nutritional care in our region, with a special focus on the MeDi for this especially vulnerable population of ...
Keywords	dietary habits ; Mediterranean diet ; diabetes ; hypertension ; chronic kidney disease ; body composition ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Vacuolar H + ATPase α3 Subunit Negatively Regulates Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cells

Mette Flinck / Sofie Hagelund / Andrej Gorbatenko / Marc Severin / Elena Pedraz-Cuesta / Ivana Novak / Christian Stock / Stine Falsig Pedersen

Cells, Vol 9, Iss 2, p

2020 Volume 465

Abstract: Increased metabolic acid production and upregulation of net acid extrusion render pH homeostasis profoundly dysregulated in many cancers. Plasma membrane activity of vacuolar H + ATPases (V-ATPases) has been implicated in acid extrusion and invasiveness ... ...

Abstract	Increased metabolic acid production and upregulation of net acid extrusion render pH homeostasis profoundly dysregulated in many cancers. Plasma membrane activity of vacuolar H + ATPases (V-ATPases) has been implicated in acid extrusion and invasiveness of some cancers, yet often on the basis of unspecific inhibitors. Serving as a membrane anchor directing V-ATPase localization, the a subunit of the V0 domain of the V-ATPase (ATP6V0a1-4) is particularly interesting in this regard. Here, we map the regulation and roles of ATP6V0a3 in migration, invasion, and growth in pancreatic ductal adenocarcinoma (PDAC) cells. a3 mRNA and protein levels were upregulated in PDAC cell lines compared to non-cancer pancreatic epithelial cells. Under control conditions, a3 localization was mainly endo-/lysosomal, and its knockdown had no detectable effect on pH i regulation after acid loading. V-ATPase inhibition, but not a3 knockdown, increased HIF-1α expression and decreased proliferation and autophagic flux under both starved and non-starved conditions, and spheroid growth of PDAC cells was also unaffected by a3 knockdown. Strikingly, a3 knockdown increased migration and transwell invasion of Panc-1 and BxPC-3 PDAC cells, and increased gelatin degradation in BxPC-3 cells yet decreased it in Panc-1 cells. We conclude that in these PDAC cells, a3 is upregulated and negatively regulates migration and invasion, likely in part via effects on extracellular matrix degradation.
Keywords	pdac ; tcirg1 ; atp6v0a3 ; invasion ; migration ; matrix degradation ; proliferation ; ph-regulation ; autophagy ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Alternating pH landscapes shape epithelial cancer initiation and progression: Focus on pancreatic cancer

Pedersen, Stine F / Ivana Novak / Frauke Alves / Albrecht Schwab / Luis A. Pardo

BioEssays. 2017 June, v. 39, no. 6

2017

Abstract: We present here the hypothesis that the unique microenvironmental pH landscape of acidâbase transporting epithelia is an important factor in development of epithelial cancers, by rendering the epithelial and stromal cells preâadapted to the ... ...

Abstract	We present here the hypothesis that the unique microenvironmental pH landscape of acidâbase transporting epithelia is an important factor in development of epithelial cancers, by rendering the epithelial and stromal cells preâadapted to the heterogeneous extracellular pH (pHâ) in the tumor microenvironment. Cells residing in organs with net acidâbase transporting epithelia such as the pancreatic ductal and gastric epithelia are exposed to very different, temporally highly variable pHâ values apically and basolaterally. This translates into spatially and temporally nonâuniform intracellular pH (pHáµ¢) patterns. Disturbed pHââ and pHáµ¢âhomeostasis contributes to essentially all hallmarks of cancer. Our hypothesis, that the physiological pHâ microenvironment in acidâbase secreting epithelia shapes cancers arising in these tissues, can be tested using novel imaging tools. The acidic tumor pHâ in turn might be exploited therapeutically. Pancreatic cancers are used as our prime example, but we propose that this concept is also relevant for other cancers of acidâbase transporting epithelia.
Keywords	epithelium ; image analysis ; landscapes ; pH ; pancreatic neoplasms ; stromal cells
Language	English
Dates of publication	2017-06
Size	p. .
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201600253
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The P2X7 receptor supports both life and death in fibrogenic pancreatic stellate cells.

Kristian A Haanes / Albrecht Schwab / Ivana Novak

PLoS ONE, Vol 7, Iss 12, p e

2012 Volume 51164

Abstract: The pancreatic stellate cells (PSCs) have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve ... ...

Abstract	The pancreatic stellate cells (PSCs) have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve whether PSCs express the multifunctional P2X7 receptor and elucidate how it regulates PSC viability. The number of PSCs isolated from wild type (WT) mice was 50% higher than those from the Pfizer P2X7 receptor knock out (KO) mice. The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs, while KO PSCs only expressed truncated versions of the receptor. In culture, the proliferation rate of the KO PSCs was significantly lower. Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs, indicating importance of endogenous ATP. Exogenous ATP had a two-sided effect. Proliferation of both WT and KO cells was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM. At high ATP concentration (5 mM), WT PSCs, but not the KO PSCs died. The intracellular Ca(2+) signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor inhibitor az10606120. The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations. This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death, and therefore might be potential targets for treatments of pancreatic fibrosis and cancer.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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