Chronic kidney disease leads to hypoxia inducible factor-1alpha to hypoxia inducible factor-2alpha switch in the gastrocnemius muscle. 2017

M Flisinski, and E Wisniewska-Chudy, and A Brymora, and A Stefanska, and P Strozecki, and J Manitius
Department of Nephrology, Hypertension and Internal Diseases, Ludwig Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland. flis3@wp.pl.

Hipoxia inducible factor-1 and HIF-2 are responsible for the adaptation of cell metabolism to hypoxia. Previously, a more severe capillary rarefaction was found in locomotor than in postural muscles of uremic animals. The aim of this study was to analyze the expression patterns of HIF and prolyl hydroxylases (PHDs) in functionally different skeletal muscles in uremic rats, an experimental model of chronic kidney disease (CKD). Rats were randomized to sham operation - CON, uninephrectomy - CKD1/2 or subtotal nephrectomy - CKD5/6. After 4 weeks, expression of HIF-1α and -2α and PHD proteins was measured using WB in locomotor, gastrocnemius muscle (MG) and postural, longissimus thoracis muscle (ML). Serum concentrations of creatinine (Cr), hemoglobin (Hb), haptoglobin (Hp), MCP-1, AGEs, homocysteine (Hcy) were measured. HIF-1α increased in MG and ML for CKD1/2 versus CON. HIF-1α decreased in MG and increased in ML for CKD5/6 versus CON and CKD1/2. HIF-2α increased in MG for CKD5/6 and CKD1/2 versus CON. HIF-2α was not detected in ML in any group. PHD1 was not detected in MG in any group. PHD1 in ML was not detected in CON, but increased in CKD5/6 and CKD1/2. PHD2 decreased in MG but increased in ML for CKD5/6 versus CKD1/2 and CON. PHD3 did not differ between groups in MG, but in ML decreased in CKD5/6 versus CON and CKD1/2. There were significant differences for CKD5/6 and CKD1/2 versus CON in: Cr (1.2 ± 0.2; 0.7 ± 0.1 versus 0.8 ± 0.3 mg/dl), Hb (11.4 ± 3.1; 13.7 ± 0.7 versus 14.1 ± 1 g/dl), Hp (1.6 ± 0.6; 1.6 ± 0.6 versus 0.7 ± 0.4 mg/ml), AGEs (5.1 ± 0.6; 4.3 ± 1.2 versus 4.6 ± 0.9 AU), Hcy (7.2 ± 1.2; 5.1 ± 0.5 versus 4.9 ± 0.5 μM), MCP-1 (609 ± 255; 489 ± 265 versus 292 ± 113 pg/ml), respectively. CKD had a different effect on protein expression patterns of HIF-1α, -2α and PHDs depending on muscle type. A HIF-1α to HIF-2α switch in glycolytic MG in CKD5/6 might be a protective mechanism against tissue hypoxia and oxidative stress.

UI MeSH Term Description Entries
D008297 Male Males
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051436 Renal Insufficiency, Chronic Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002) Kidney Insufficiency, Chronic,Chronic Kidney Diseases,Chronic Kidney Insufficiency,Chronic Renal Diseases,Chronic Renal Insufficiency,Chronic Kidney Disease,Chronic Kidney Insufficiencies,Chronic Renal Disease,Chronic Renal Insufficiencies,Disease, Chronic Kidney,Disease, Chronic Renal,Diseases, Chronic Kidney,Diseases, Chronic Renal,Kidney Disease, Chronic,Kidney Diseases, Chronic,Kidney Insufficiencies, Chronic,Renal Disease, Chronic,Renal Diseases, Chronic,Renal Insufficiencies, Chronic
D051792 Basic Helix-Loop-Helix Transcription Factors A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF. Basic Helix-Loop-Helix Transcription Factor,bHLH Protein,bHLH Transcription Factor,bHLH Proteins,bHLH Transcription Factors,Basic Helix Loop Helix Transcription Factor,Basic Helix Loop Helix Transcription Factors,Factor, bHLH Transcription,Protein, bHLH,Transcription Factor, bHLH,Transcription Factors, bHLH
D051795 Hypoxia-Inducible Factor 1, alpha Subunit Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN. Hypoxia Inducible Factor 1, alpha Subunit
D018398 Homeodomain Proteins Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL). Homeo Domain Protein,Homeobox Protein,Homeobox Proteins,Homeodomain Protein,Homeoprotein,Homeoproteins,Homeotic Protein,Homeo Domain Proteins,Homeotic Proteins,Domain Protein, Homeo,Protein, Homeo Domain,Protein, Homeobox,Protein, Homeodomain,Protein, Homeotic,Proteins, Homeo Domain,Proteins, Homeobox,Proteins, Homeodomain,Proteins, Homeotic
D018482 Muscle, Skeletal A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles

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