A5029786079- Cancer-related gene regulation
- Connective tissue disorders research
- Cancer, Hypoxia, and Metabolism
- Bone and Dental Protein Studies
- Ubiquitin and proteasome pathways
- Aldose Reductase and Taurine
- Cell Adhesion Molecules Research
- Collagen: Extraction and Characterization
- Microbial metabolism and enzyme function
- Wnt/β-catenin signaling in development and cancer
- S100 Proteins and Annexins
- Urological Disorders and Treatments
- Genetic Neurodegenerative Diseases
- High Altitude and Hypoxia
- Neurogenetic and Muscular Disorders Research
- Osteoarthritis Treatment and Mechanisms
- Enzyme Structure and Function
- Adipose Tissue and Metabolism
- Iron and Steelmaking Processes
- Protein Structure and Dynamics
- Endoplasmic Reticulum Stress and Disease
- Protease and Inhibitor Mechanisms
- Tissue Engineering and Regenerative Medicine
- Metabolism, Diabetes, and Cancer
- Medical Imaging and Pathology Studies
University of Oulu
2007-2024
Biocenter Finland
2006-2015
Matrix Research (United States)
2015
Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of triple helical domain collagens. P4HA1 encodes catalytic α(I) subunit main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic mutations family with congenital-onset disorder connective tissue, manifesting as early-onset joint hypermobility, contractures, muscle weakness bone dysplasia well high myopia, evidence clinical improvement motor function over time surviving patient. Similar to...
The Wnts can be considered as candidates for the Congenital Anomaly of Kidney and Urinary Tract, CAKUT diseases since they take part in control kidney organogenesis. Of them Wnt5a is expressed ureteric bud (UB) its deficiency leads to duplex collecting system (13/90) uni- or bilateral agenesis (10/90), hypoplasia with altered pattern tree organization (42/90) lobularization defects partly fused ureter trunks (25/90) unlike controls. UB had also notably less tips due being at E15.5 306 E16.5...
Collagen biosynthesis requires several co- and post-translational modifications of lysine proline residues to form structurally functionally competent collagen molecules. Formation 4-hydroxyproline (4Hyp) in Y-position prolines the repetitive -X-Y-Gly- sequences provides thermal stability for triple-helical 4Hyp formation is catalyzed by a prolyl 4-hydroxylase (C-P4H) family consisting three isoenzymes. Here we identify specific roles two main C-P4H isoenzymes hydroxylation detailed analysis...
Collagen is the most abundant protein in humans. It has a characteristic triple-helix structure and heavily posttranslationally modified. The complex biosynthesis of collagen involves processing by many enzymes chaperones rough endoplasmic reticulum. Lysyl hydroxylase 1 (LH1) required to hydroxylate lysine for cross-linking carbohydrate attachment within triple helical sequences. Additionally, recent study prolyl 3-hydroxylase 3 (P3H3) demonstrated that this enzyme may be critical LH1...
Proper deposition of the extracellular matrix and its major components, collagens, is essential for endochondral ossification bone mass accrual. Collagen prolyl 4-hydroxylases (C-P4Hs) hydroxylate proline residues in -X-Pro-Gly- repeats all known collagen types. Their product, 4-hydroxyproline, correct folding thermal stability triple-helical molecules physiological body temperatures. We have previously shown that inactivation mouse
Collagen prolyl 4-hydroxylases (C-P4H) are α2β2 tetramers, which catalyze the 4-hydroxylation of procollagen, allowing for formation stable triple-helical collagen structure in endoplasmic reticulum. The C-P4H α-subunit provides N-terminal dimerization domain, middle peptide-substrate-binding (PSB) and C-terminal catalytic (CAT) whereas β-subunit is identical to enzyme protein disulfide isomerase (PDI). part (N-terminal region PSB domain) known, but structures PSB-CAT linker CAT domain as...
Abstract Transmembrane prolyl 4-hydroxylase (P4H-TM) is an enigmatic enzyme whose cellular function and primary substrate remain to be identified. Its loss-of-function mutations cause a severe neurological HIDEA syndrome with hypotonia, intellectual disability, dysautonomia hypoventilation. Previously, P4H-TM deficiency in mice was associated reduced atherogenesis lower serum triglyceride levels. Here, we characterized the glucose lipid metabolism of P4h-tm −/− physiological tissue analyses....
Age-related macular degeneration (AMD), affecting the retinal pigment epithelium (RPE), is leading cause of blindness in middle-aged and older people developed countries. Genetic environmental risk factors have been identified, but no effective cure exists. Using a mouse model we show that transmembrane prolyl 4-hydroxylase (P4H-TM), which participates oxygen-dependent regulation hypoxia-inducible factor (HIF), potential novel candidate gene for AMD. We P4h-tm had its highest expression...
Background Collagen XIII is a transmembrane collagen associated with neuromuscular junction development, and in humans its deficiency results congenital myasthenic syndrome type 19 (CMS19), which leads to breathing difficulties. CMS19 patients usually have restricted lung capacity one patient developed chronic disease. In single-cell RNA sequencing studies, has been identified as marker for pulmonary lipofibroblasts, implicated the resolution of fibrosis. Methods We investigated location...
ABSTRACT Formation of 4-hydroxyproline (4Hyp) in -X-Pro-Gly- collagen sequences is essential for the thermal stability molecules. 4Hyp formation catalyzed by prolyl 4-hydroxylases (C- P4H). Here we identify specific roles two main C-P4H isoenzymes analysis type I and IV collagens. Loss C-P4H-I mainly affected prolines preceded an X-position amino acid with a positively charged or polar uncharged side chain. In contrast, loss C-P4H-II triplets negatively glutamate aspartate X-position, their...
Material efficiency is one of the most effective methods for achieving more sustainable operations in iron and steelmaking. Sintering briquetting processes are commonly used integrated steel plants to recycle carbon- iron-containing residues back blast furnace. In Ruukki steelworks Finland, a surplus solid coking plant by-products produced, none which presently utilized within steelworks. this paper, novel concept recycling furnace via liquid-solid injection evaluated. According conducted...
The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful mechanism regulating cellular adaptation to decreased oxygenation. gastrointestinal epithelium subsists in “physiological hypoxia” and should therefore have an especially well-designed over this adaptation. Thus, we assessed the absolute mRNA expression levels of pathway components, Hif1a, HIF2a, Hif-p4h-1, 2 3 inhibiting (Fih1) murine jejunum, caecum colon using droplet digital PCR. We found higher...
Abstract Collagen is the most abundant protein in humans and heavily post-translationally modified. Its biosynthesis very complex requires three different types of hydroxylation (two for proline one lysine) that are generated rough endoplasmic reticulum (rER). These processes involve many enzymes chaperones which were collectively termed molecular ensemble collagen biosynthesis. However, function some proteins this controversial. While prolyl 3-hydroxylase 1 2 (P3H1, P3H2) bona fide...