Seppo Parkkila

Seppo Parkkila
Tampere University | UTA · Faculty of Medicine and Health Technology

MD, PhD

About

408
Publications
34,408
Reads
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16,579
Citations
Additional affiliations
January 2002 - September 2020
Tampere University
Position
  • Professor
May 1996 - April 1998
Saint Louis University
January 1991 - December 2001
Oulu University Hospital
Education
March 1991 - May 2001
University of Oulu
Field of study
  • Clinical Chemistry
January 1990 - December 1994
University of Oulu
Field of study
  • Anatomy
August 1985 - February 1991
University of Oulu
Field of study
  • Medicine

Publications

Publications (408)
Article
Inadequate diet and frequent symptomatic infections are considered major causes of growth stunting in low-income countries, but interventions targeting these risk factors have achieved limited success. Asymptomatic infections can restrict growth, but little is known about their role in global stunting prevalence. We investigated factors related to...
Article
The α-class carbonic anhydrase (CA, EC 4.2.1.1) from the protozoan pathogen Trypanosoma cruzi, TcCA, was investigated earlier for its inhibition with anions, sulphonamides, thiols and hydroxamates, well-known classes of CA inhibitors (CAIs). Here we present the first inhibition study of this enzyme with phenols, which possess a diverse CA inhibitio...
Article
Full-text available
Carbonic anhydrases (CA, EC 4.2.1.1) catalyze the hydration of carbon dioxide and take part in many essential physiological processes. In humans, 15 CAs are characterized, including the only secreted isoenzyme CA VI. CA VI has been linked to specific processes in the mouth, namely bitter taste perception, dental caries, and maintenance of enamel pe...
Article
Full-text available
Background Malaria is a significant parasitic infection, and human infection is mediated by mosquito ( Anopheles ) biting and subsequent transmission of protozoa ( Plasmodium ) to the blood. Carbonic anhydrases (CAs) are known to be highly expressed in the midgut and ectoperitrophic space of Anopheles gambiae . Transmembrane CAs (tmCAs) in Plasmodi...
Article
Full-text available
We report the production and biochemical characterization of an α-carbonic anhydrase (LrhCA) from gram-positive probiotic bacteria Lactobacillus rhamnosus GG. CAs form a family of metalloenzymes that catalyze hydration of CO2/interconversion between CO2 and water to bicarbonate ions and protons. They are divided into eight independent gene families...
Article
A b-class carbonic anhydrase (CA, EC 4.2.1.1) was cloned from the genome of the Monogenean platyhel-minth Gyrodactylus salaris, a parasite of Atlantic salmon. The new enzyme, GsaCAb has a significant catalytic activity for the physiological reaction, CO 2 þ H 2 O HCO 3 À þ H þ with a k cat of 1.1 Â 10 5 s À1 and a k cat /K m of 7.58 Â 10 6 M À1 Â s...
Article
The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat. Despite strict control measures implemented worldwide and immunization using novel vaccines, the pandemic continues to rage due to emergence of several variants of SARS-CoV-2 with increased transmission and immune escape....
Article
Full-text available
Background The pathogenesis of gastroesophageal reflux disease (GERD) has not been resolved in detail. Esophageal epithelial cells provide resistance to acidic reflux via several mechanisms, many of which involve buffering acid with bicarbonate and transporting protons. Carbonic anhydrases (CAs) are enzymes that control the acid–base balance by cat...
Article
Full-text available
During recent decades, zebrafish (Danio rerio) have become one of the most important model organisms in which to study different physiological and biological phenomena. The research field of carbonic anhydrases (CAs) and carbonic anhydrase related proteins (CARPs) is not an exception to this. The best-known function of CAs is the regulation of acid...
Preprint
During the last decades, zebrafish (Danio rerio) has become one of the most important model organisms to study different physiological and biological phenomena. Research field of carbonic anhydrases (CAs) and carbonic anhydrase related proteins (CARPs) is not an exception in this. The best-known known function of CAs is the regulation of acid-base...
Article
During the past three decades, mice, zebrafish, fruit flies, and Caenorhabditis elegans have been the primary model organisms used for the study of various biological phenomena. These models have also been adopted and developed to investigate the physiological roles of carbonic anhydrases (CAs) and carbonic anhydrase-related proteins (CARPs). These...
Article
Full-text available
Trichomonas vaginalis is a unicellular parasite and responsible for one of the most common sexually transmittable infections worldwide, trichomoniasis. Carbonic anhydrases (CAs) are enzymes found in all lifeforms and are known to play a vital role in many biochemical processes in organisms including the maintenance of acid–base homeostasis. To date...
Article
Full-text available
Sulphonamides and their isosteres are classical inhibitors of the carbonic anhydrase (CAs, EC 4.2.1.1) metalloenzymes. The protozoan pathogen Trichomonas vaginalis encodes two such enzymes belonging to the β-class, TvaCA1 and TvaCA2. Here we report the first sulphonamide inhibition study of TvaCA1, with a series of simple aromatic/heterocyclic prim...
Article
Full-text available
We report the first activation study of the β-class carbonic anhydrase (CA, EC 4.2.1.1) encoded in the genome of the protozoan pathogen Trichomonas vaginalis, TvaCA1. Among 24 amino acid and amine activators investigated, derivatives incorporating a second carboxylic moiety, such as L-Asp, L- and D-Glu, were devoid of activating effects up to conce...
Article
Full-text available
Pathogenic bacteria resistant to most antibiotics, including the methicillin-resistant Staphylococcus aureus (MRSA) represent a serious medical problem. The search for new antiinfectives, possessing a diverse mechanism of action compared to the clinically used antibiotics, has become an attractive research field. S. aureus DNA encodes a β-class car...
Chapter
The early immunohistochemical studies of carbonic anhydrases (CAs) were mainly focused on their normal tissue distribution. Only a few studies included samples from pathologic diseases, particularly cancer. This line of research remained inactive until the discovery of CA IX—the first cancer-associated isozyme. The association of CA IX with hypoxic...
Chapter
Carbonic anhydrases (CAs) are widely expressed in the nervous system where they play important physiological roles. In the brain and other parts of the system, different isozymes show unique distribution patterns, some of them being present in neurons (CA II, V, VII, XIV), capillary endothelium (CA IV), microglia (CA III), choroid plexus (CA II, II...
Chapter
Trichomonas vaginalis is a unicellular parasite responsible for trichomoniasis, which is one of the world’s leading sexually transmitted infections (STIs). The diagnosis and effective treatment of trichomoniasis has become an extremely important goal for global health, due to the increasing experimental evidences showing the relationship between tr...
Article
Non-ampullary duodenal adenocarcinoma (DAC) is a rare malignancy. Little information is available concerning the histopathological prognostic factors associated with DAC. Carbonic anhydrases (CAs) are metalloenzymes catalyzing the universal reaction of CO2 hydration. Isozymes CAII, CAIX, and CAXII are associated with prognosis in various cancers. O...
Chapter
Entamoeba histolytica infection, amoebiasis, is a major cause of morbidity and mortality in developing countries. It is also a significant causative agent of traveler’s diarrhea. It has been estimated that amoebiasis may affect 10% of the global population. The most common infection route is via ingestion of contaminated food and water. About 90% o...
Article
Full-text available
Introduction: The coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide and vaccination remains the most effective approach to control COVID-19. Currently, at least ten COVID-19 vaccines have been authorized under emergency authorization. However, these vaccines still face many challenges, such as the emergence of variant strai...
Article
Full-text available
Sus scrofa or pig was domesticated thousands of years ago. Through various indigenous breeds, different phenotypes were produced such as Chinese inbred miniature minipig or Wuzhishan pig (WZSP), which is broadly used in the life and medical sciences. The whole genome of WZSP was sequenced in 2012. Through a bioinformatics study of pig carbonic anhy...
Chapter
Trichomoniasis is the most common sexually transmitted protozoan infection, which has been treated for several decades using nitroimidazoles, mainly metronidazole and tinidazole. Both drugs are still recommended and resistance to them has fortunately been a relatively rare phenomenon. Resistant or tolerant cases exist, however, side effects are als...
Article
Full-text available
Bacillus Calmette-Guérin (BCG) is a live attenuated M. bovis vaccine that was developed about 100 years ago by Albert Calmette and Camille Guérin. Many countries have been using the vaccine for decades against tuberculosis (TB). The World Health Organization (WHO) recommends a single dose of BCG for infants in TB endemic as well as leprosy high ris...
Article
Full-text available
Bacillus Calmette-Guérin (BCG) is a live attenuated M. bovis vaccine that was developed about 100 years ago by Albert Calmette and Camille Guérin. Many countries have been using the vaccine for decades against tuberculosis (TB). The world Health Organization (wHO) recommends a single dose of BCG for infants in TB endemic as well as leprosy high...
Chapter
It has been widely studied that cancer thrives in hypoxic conditions. The importance of tumor metabolism was already discovered in the 1930s by Otto H. Warburg, and the Warburg effect is described by the ability of cancer cells to ferment sugars independently of the oxygen levels. Yet, there is still a lack of understanding of the mechanisms behind...
Article
Full-text available
We report the biochemical and structural characterisation of a beta-carbonic anhydrase (β-CA) from Trichomonas vaginalis, a unicellular parasite responsible for one of the world’s leading sexually transmitted infections, trichomoniasis. CAs are ubiquitous metalloenzymes belonging to eight evolutionarily divergent groups (α, β, γ, δ, ζ, η, θ, and ι)...
Article
Full-text available
This paper presents the production and kinetic and inhibitory characterisation of β-carbonic anhydrase from the opportunistic bacterium Staphylococcus aureus (SauBCA). From the eight different carbonic anhydrase (CA) families known to date, humans have only the α-form, whereas many clinically relevant pathogens have β- and/or γ-form(s). Based on th...
Article
The protozoan pathogen Trichomonas vaginalis encodes two carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the β-class. One of these enzymes, T. vaginalis carbonic anhydrase 1 (TvaCA1), was recently cloned and characterized by our group, and its X-ray crystal structure reported. No inhibitors of this enzyme were reported up until now. Here we inve...
Article
Full-text available
The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics too...
Article
Full-text available
Parvalbumins are the most important fish allergens, which are heat-stable, classified in the family of calcium-binding EF-hand proteins, and contain one magnesium binding site. The functional connection between calcium and parvalbumin gives fish the high-speed swimming ability because of high concentration of Ca2+-binding parvalbumin in fish white...
Article
Full-text available
Here, we report a toxicity study, conducted on zebrafish larvae, of a series of coumarin and sulfamide compounds that were previously reported as inhibitors of human (h) metalloenzymes, carbonic anhy-drases (CAs, EC 4.2.1.1). Due to the high relevance of hCA inhibitors as theragnostic agents, it is of pivotal importance to address safety issues tha...
Preprint
Full-text available
Transcription factor (TF) proteins play a critical role in the regulation of eukaryote gene expression by sequence-specific binding to genomic locations known as transcription factor binding sites. Here we present the TFBSFootprinter tool which has been created to combine transcription-relevant data from six large empirical datasets: Ensembl, JASPA...
Article
Full-text available
Carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. CA VI is secreted to milk and saliva, and it could contribute to wound closure, as a potential trophic factor, in animals that typically lick their wounds. Our aim was to investigate...
Article
Full-text available
Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that participate in the regulation of pH homeostasis in addition to many other important physiological functions. Importantly, CAs have been associated with neoplastic processes and cancer. Brain tumors represent a heterogeneous group of diseases with a frequently dismal prognosis, and ne...
Article
Full-text available
Hypoxia, a common feature of solid tumours' microenvironment, is associated with an aggressive phenotype and is known to cause resistance to anticancer chemo-and radiotherapies. Tumour-associated carbonic anhydrases isoform IX (hCA IX), which is upregulated under hypoxia in many malignancies participating to the microenvironment acidosis, represent...
Article
Full-text available
Background: The inaccuracy of DNA sequence data is becoming a serious problem, as the amount of molecular data is multiplying rapidly and expectations are high for big data to revolutionize life sciences and health care. In this study, we investigated the accuracy of DNA sequence data from commonly used databases using carbonic anhydrase (CA) gene...
Preprint
Full-text available
The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics too...
Article
We report for the first time, a novel series of telluride bearing sulfonamide as selective and potent inhibitors of the β-class Carbonic Anhydrase (CA; EC 4.2.1.1) enzyme expressed in Leishmania donovani protozoa. Such derivatives showed high activity against axenic amastigotes, and among them compound 5g showed an IC50 of 0.02 µM being highly sele...
Article
Full-text available
On June 13, 2018 a consensus meeting of the PhD degree in medicine and dentistry was held in Oulu to review the prevailing practices and assess the needs for change. The PhD degree should be completed in four years of full­time work and, except for one university, is formally awarded by the respective faculty. There are typically two or three super...
Article
Full-text available
With the aim to obtain novel compounds possessing both strong affinity against human carbonic anhydrases and low toxicity, we synthesised novel thiourea and sulphonamide derivatives 3, 4 and 10, and studied their in vitro inhibitory properties against human CA I, CA II and CA IX. We also evaluated the toxicity of these compounds using zebrafish lar...
Article
Full-text available
We investigated a panel of 14 compounds belonging to the monothiocarbamate (MTC) and dithiocarbamate (DTC) series against the β-carbonic anhydrase 3 (β-CA3) of Mycobacterium tuberculosis (Mtb). We also evaluated all compounds for toxicity using 1–5-day post fertilisation zebrafish embryos. 11 out of the 14 investigated derivatives showed effective...
Article
Full-text available
Trypanosoma cruzi carbonic anhydrase (TcCA) has recently emerged as an interesting target for the design of new compounds to treat Chagas disease. In this study we report the results of a structure-based virtual screening campaign to identify novel and selective TcCA inhibitors. The combination of properly validated computational methodologies such...
Article
Full-text available
The genome of Mycobacterium tuberculosis (Mtb) encodes three β-carbonic anhydrases (CAs, EC 4.2.1.1) that are crucial for the life cycle of the bacterium. The Mtb β-CAs have been cloned and characterized, and the catalytic activities of the enzymes have been studied. The crystal structures of two of the enzymes have been resolved. In vitro inhibiti...
Article
Full-text available
Secretory human carbonic anhydrase VI (CA VI) has emerged as a potential drug target due to its role in pathological states, such as excess acidity-caused dental caries and injuries of gastric epithelium. Currently, there are no available CA VI-selective inhibitors or crystallographic structures of inhibitors bound to CA VI. The present study focus...
Data
Screening of CA inhibitors for neurotoxicity using zebrafish larval model. The CA inhibitor compound showed sedatory effect but no toxicity and could be characterized further.
Article
Full-text available
Long non-coding RNAs (lncRNAs) are classified as a group of transcripts which regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between ln...
Chapter
Full-text available
Carbonic anhydrase (CA) IX belongs to a group of druggable targets which significantly affect cancer progression. Although many CA IX-targeting compounds have been reported, only a few sulfonamide derivatives progressed to clinical trials, and the results have been unfavorable, or unavailable, so far. Therefore, the design of different, more effici...
Article
Full-text available
Carbonic anhydrases (CA) catalyze the reversible hydration of CO2 to protons and bicarbonate, and thereby play a fundamental role in the epithelial acid‐base transport mechanisms serving fluid secretion and absorption for whole body acid‐base regulation. The three carbonic anhydrase‐related proteins (CARPs) VIII, X, and XI, however, are catalytical...
Article
The zebrafish is a widely used vertebrate model organism for disease and phenotye-based drug discovery. The zebrafish has many unique features, including large number of offspring, transparent embryos and rapid external development. Zebrafish embryos can therefore also be used for rapid evaluation of toxicity of the drugs that are precious and avai...
Article
Full-text available
Wounds close by keratinocytes migrating from the edge of the wound and re‐epithelializing the epidermis. It has been proposed that the major stimuli for wound closure are blood‐derived growth factors, chemokines, and cytokines. The small GTPase R‐Ras, a known integrin activator, also regulates vascular permeability during angiogenesis, and blood ve...
Article
Full-text available
The β-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic protozoan Entamoeba histolytica, EhiCA, was investigated for its activation with a panel of natural and non-natural amino acids and amines. EhiCA was potently activated by D-His, D-Phe, D-DOPA, L- and D-Trp, L- and D-Tyr, 4-amino-L-Tyr, histamine and serotonin, with KAs ranging between 1...
Chapter
Abstract Protozoan pathogens are major contributors to illness and death globally. Much of their impact can be controlled by a few drugs that are available. The resistance of these organisms to the existing drugs has threatened the treatment options. Therefore, many efforts are taken worldwide to develop drugs targeting novel pathways of protozoan...
Article
Full-text available
A newly described β-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic protozoan Entamoeba histolytica, EhiCA, was recently shown to possess a significant catalytic activity for the physiologic CO2 hydration reaction (kcat of 6.7 × 105 s−1 and a kcat/Km of 8.9 × 107 M−1 s−1). A panel of sulphonamides and one sulfamate, some of which are clinic...
Article
Full-text available
An anion inhibition study of the β-class carbonic anhydrase, AgaCA, from the malaria mosquito Anopheles gambiae is reported. A series of simple as well as complex inorganic anions, and small molecules known to interact with CAs were included in the study. Bromide, iodide, bisulphite, perchlorate, perrhenate, perruthenate, and peroxydisulphate were...
Article
Full-text available
We report the cloning and catalytic activity of a β-carbonic anhydrase (CA, EC 4.2.1.1), isolated from the pathogenic protozoan Entamoeba histolytica, EhiCA. This enzyme has a high catalytic activity for the physiologic CO2 hydration reaction, with a kcat of 6.7 × 105 s−1 and a kcat/Km of 8.9 × 107 M−1 × s−1. An anion inhibition study of EhiCA with...
Poster
Full-text available
The poster presented the work carried out using zebrafish model for developing novel anti-TB drugs.
Poster
Full-text available
Introduction: Transcription factors (TFs) are the primary actors of gene expression and regulation. A genome-wide understanding of their targets will have significant benefits in many biological studies. However, due to the time and monetary cost of direct experimentation we possess little knowledge as to which TFs influence the expression of most...
Poster
Full-text available
Introduction: Transcription factors (TFs) are the primary actors of gene expression and regulation. A genome-wide understanding of their targets will have significant benefits in many biological studies. However, due to the time and monetary cost of direct experimentation we possess little knowledge as to which TFs influence the expression of most...