9 research outputs found

    GSK3β Serine 389 Phosphorylation Modulates Cardiomyocyte Hypertrophy and Ischemic Injury

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    Prior studies show that glycogen synthase kinase 3β (GSK3β) contributes to cardiac ischemic injury and cardiac hypertrophy. GSK3β is constitutionally active and phosphorylation of GSK3β at serine 9 (S9) inactivates the kinase and promotes cellular growth. GSK3β is also phosphorylated at serine 389 (S389), but the significance of this phosphorylation in the heart is not known. We analyzed GSK3β S389 phosphorylation in diseased hearts and utilized overexpression of GSK3β carrying ser→ala mutations at S9 (S9A) and S389 (S389A) to study the biological function of constitutively active GSK3β in primary cardiomyocytes. We found that phosphorylation of GSK3β at S389 was increased in left ventricular samples from patients with dilated cardiomyopathy and ischemic cardiomyopathy, and in hearts of mice subjected to thoracic aortic constriction. Overexpression of either GSK3β S9A or S389A reduced the viability of cardiomyocytes subjected to hypoxia–reoxygenation. Overexpression of double GSK3β mutant (S9A/S389A) further reduced cardiomyocyte viability. Determination of protein synthesis showed that overexpression of GSK3β S389A or GSK3β S9A/S389A increased both basal and agonist-induced cardiomyocyte growth. Mechanistically, GSK3β S389A mutation was associated with activation of mTOR complex 1 signaling. In conclusion, our data suggest that phosphorylation of GSK3β at S389 enhances cardiomyocyte survival and protects from cardiomyocyte hypertrophy

    GSK3β Serine 389 Phosphorylation Modulates Cardiomyocyte Hypertrophy and Ischemic Injury

    Get PDF
    Prior studies show that glycogen synthase kinase 3β (GSK3β) contributes to cardiac ischemic injury and cardiac hypertrophy. GSK3β is constitutionally active and phosphorylation of GSK3β at serine 9 (S9) inactivates the kinase and promotes cellular growth. GSK3β is also phosphorylated at serine 389 (S389), but the significance of this phosphorylation in the heart is not known. We analyzed GSK3β S389 phosphorylation in diseased hearts and utilized overexpression of GSK3β carrying ser→ala mutations at S9 (S9A) and S389 (S389A) to study the biological function of constitutively active GSK3β in primary cardiomyocytes. We found that phosphorylation of GSK3β at S389 was increased in left ventricular samples from patients with dilated cardiomyopathy and ischemic cardiomyopathy, and in hearts of mice subjected to thoracic aortic constriction. Overexpression of either GSK3β S9A or S389A reduced the viability of cardiomyocytes subjected to hypoxia–reoxygenation. Overexpression of double GSK3β mutant (S9A/S389A) further reduced cardiomyocyte viability. Determination of protein synthesis showed that overexpression of GSK3β S389A or GSK3β S9A/S389A increased both basal and agonist-induced cardiomyocyte growth. Mechanistically, GSK3β S389A mutation was associated with activation of mTOR complex 1 signaling. In conclusion, our data suggest that phosphorylation of GSK3β at S389 enhances cardiomyocyte survival and protects from cardiomyocyte hypertrophy

    Sufficiency of Knowledge Processed in Patient Education in Dialysis Care

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    Purpose: Patient education improves health and treatment adherence of patients with chronic kidney disease. However, evidence about the sufficiency of patients’ knowledge processed in patient education is limited. The purpose of this study was to evaluate subjective and objective sufficiency of knowledge processed in patient education in dialysis care and treatment.Patients and Methods: A cross-sectional study design was used. The sample (n=162) comprised patients in predialysis or home dialysis. All eligible patients during the data collection timeframe (2016– 2017) in two university hospital districts in Finland were invited to participate. Subjective sufficiency was evaluated with a structured questionnaire having 34 items divided into six dimensions of empowering knowledge (bio-physiological, functional, social, experiential, ethical, and financial) on a Likert scale (1=not sufficient at all, 4=very sufficient). Objective sufficiency was evaluated with a structured knowledge test with 10 items (score range 0– 10, correct=1, wrong/no knowledge=0) based on the multidimensional content of patient education emphasizing bio-physiological dimension.Results: In subjective sufficiency of knowledge, the mean was 3.27 (SD 0.54). The bio-physiological dimension of empowering knowledge was the most sufficient (mean 3.52, SD 0.49) and the experiential the least (mean 2.8, SD 0.88). In objective sufficiency, the means ranged 5.15– 5.97 (SD 2.37– 2.68) among patients in different modalities of dialysis care and treatment. The least sufficient objective scores were bio-physiological and functional knowledge. The subjective and objective sufficiency did not correlate with each other.Conclusion: Patients’ knowledge, either subjective or objective, does not seem to be sufficient. Hence, attention should be paid to supporting patients with more personalized knowledge. Furthermore, the relationship between subjective and objective sufficiency needs future consideration, as their non-correspondence was a new discovery.Keywords: chronic kidney disease, hemodialysis, home, patient education as topic, peritoneal dialysis, renal dialysis </p

    GSK3β Serine 389 Phosphorylation Modulates Cardiomyocyte Hypertrophy and Ischemic Injury

    Get PDF
    Prior studies show that glycogen synthase kinase 3&beta; (GSK3&beta;) contributes to cardiac ischemic injury and cardiac hypertrophy. GSK3&beta; is constitutionally active and phosphorylation of GSK3&beta; at serine 9 (S9) inactivates the kinase and promotes cellular growth. GSK3&beta; is also phosphorylated at serine 389 (S389), but the significance of this phosphorylation in the heart is not known. We analyzed GSK3&beta; S389 phosphorylation in diseased hearts and utilized overexpression of GSK3&beta; carrying ser&rarr;ala mutations at S9 (S9A) and S389 (S389A) to study the biological function of constitutively active GSK3&beta; in primary cardiomyocytes. We found that phosphorylation of GSK3&beta; at S389 was increased in left ventricular samples from patients with dilated cardiomyopathy and ischemic cardiomyopathy, and in hearts of mice subjected to thoracic aortic constriction. Overexpression of either GSK3&beta; S9A or S389A reduced the viability of cardiomyocytes subjected to hypoxia&ndash;reoxygenation. Overexpression of double GSK3&beta; mutant (S9A/S389A) further reduced cardiomyocyte viability. Determination of protein synthesis showed that overexpression of GSK3&beta; S389A or GSK3&beta; S9A/S389A increased both basal and agonist-induced cardiomyocyte growth. Mechanistically, GSK3&beta; S389A mutation was associated with activation of mTOR complex 1 signaling. In conclusion, our data suggest that phosphorylation of GSK3&beta; at S389 enhances cardiomyocyte survival and protects from cardiomyocyte hypertrophy

    Systemic Blockade of ACVR2B Ligands Protects Myocardium from Acute Ischemia-Reperfusion Injury

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    Activin A and myostatin, members of the transforming growth factor (TGF)-b superfamily of secreted factors, are potent negative regulators of muscle growth, but their contribution to myocardial ischemia-reperfusion (IR) injury is not known. The aim of this study was to investigate if activin 2B (ACVR2B) receptor ligands contribute to myocardial IR injury. Mice were treated with soluble ACVR2B decoy receptor (ACVR2B-Fc) and subjected to myocardial ischemia followed by reperfusion for 6 or 24 h. Systemic blockade of ACVR2B ligands by ACVR2B-Fc was protective against cardiac IR injury, as evidenced by reduced infarcted area, apoptosis, and autophagy and better preserved LV systolic function following IR. ACVR2B-Fc modified cardiac metabolism, LV mitochondrial respiration, as well as cardiac phenotype toward physiological hypertrophy. Similar to its protective role in IR injury in vivo, ACVR2B-Fc antagonized SMAD2 signaling and cell death in cardiomyocytes that were subjected to hypoxic stress. ACVR2B ligand myostatin was found to exacerbate hypoxic stress. In addition to acute cardioprotection in ischemia, ACVR2B-Fc provided beneficial effects on cardiac function in prolonged cardiac stress in cardiotoxicity model. By blocking myostatin, ACVR2B-Fc potentially reduces cardiomyocyte death and modifies cardiomyocyte metabolism for hypoxic conditions to protect the heart from IR injury.Peer reviewe

    Syväjohtamisen toteutuminen Suomen toimintaterapia-alalla

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    Tarkoituksena tässä tutkimuksessa oli kuvata syväjohtajuuden ulottuvuuksien toteutumista toimintaterapia-alan johtajilla Suomessa. Työntekijät arvioivat lähijohtajiensa johtajuuskäyttäytymistä. Toimintaterapia-alan organisaatioihin kuuluvat tässä tutkimuksessa koulutusalan, yksityisen ja julkisen sektorin lisäksi kolmannen sektorin. Johtajuuskäyttäytymisen elementit pitävät sisällään luottamuksen rakentamisen, inspiroivan tavan motivoida, älyllisen stimuloinnin, ihmisen yksilöllinen kohtaamisen, tavoitteellisen johtamisen, kontrolloivan johtamisen ja passiivisen johtamisen. Tutkimuksen kohderyhmän muodostivat suomalaisten toimintaterapiaorganisaatioiden työntekijät, joilla on lähiesimies. Tutkimusaineisto kerättiin sähköisesti TOINET-ammatillisen nettiverkoston avulla käyttämällä Nissisen (2001) kehittämää työyhteisöprofiili kysymyssarjaa. Mittari koostui 30 väittämästä. Kyselylomakkeessa oli kolme osaa, taustamuuttujat, 30 vaihtoehtokysymystä Likertin asteikolla (0-4) sekä kolme avointa kysymystä. Vastausmäärä kyselyyn oli 128 kappaletta. Tilastollinen käsittely ja analysointi tapahtui SPSS 18.0 ohjelmalla. Aineistosta laskettiin frekvenssit, prosenttijakaumat, keskiarvot ja keskihajonnat. Mittarin osioista muodostettiin summamuuttujat ja niiden yhteneväisyys testattiin käyttämällä Cronbachin Alfa -kerrointa. Tilastollisina menetelminä käytettiin Spearmannin korrelaatiokerrointa, Mann-Whitneyn U-testiä, Kruskall-Wallsin testiä sekä varianssianalyysiä. Tutkimuksen tuloksena syväjohtajuuden ulottuvuuksista esiintyi tämän tutkimuksen perusteella toimintaterapia-alalla eniten ihmisten yksilöllistä kohtaamista, luottamuksen rakentamista sekä tavoitteellista johtamista lähes yhtä paljon. Älyllistä stimulointia esiintyi syväjohtamisen ulottuvuuksista vähiten. Passiivista johtajuutta esiintyi johtajuusulottuvuuksista kaikkein vähiten. Ylimmällä koulutuksella oli tilastollisesti merkitsevä vaikutusjohtamiskäyttäytymiseen inspiroivaan tapaan motivoida. Organisaation laadulla oli tilastollisesti merkittävä yhteys samaan syväjohtajuuden ulottuvuuteen inspiroivaan tapaan motivoida. Organisaation laadulla oli myös tilastollisesti merkittävä yhteys kontrolloivaan johtajuuteen. Avoimien kysymysten perusteella toimintaterapia-alan johtajuuden kehittämisalueina olivat luottamuksellisuus, työntekijän ja hänen työnsä arvostaminen, tasapuolisuus, tavoitteellisuus, vuorovaikutuksen selkeys ja laatu sekä asettuminen työntekijän asemaan. Muita alueita olivat kyselyn perusteella lisäksi johtajan itsetunnon vahvistuminen, työntekijän motivointi ja arvopohjan vahvistuminen

    Sufficiency of Knowledge Processed in Patient Education in Dialysis Care

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    Purpose: Patient education improves health and treatment adherence of patients with chronic kidney disease. However, evidence about the sufficiency of patients' knowledge processed in patient education is limited. The purpose of this study was to evaluate subjective and objective sufficiency of knowledge processed in patient education in dialysis care and treatment. Patients and Methods: A cross-sectional study design was used. The sample (n=162) comprised patients in predialysis or home dialysis. All eligible patients during the data collection timeframe (2016-2017) in two university hospital districts in Finland were invited to participate. Subjective sufficiency was evaluated with a structured questionnaire having 34 items divided into six dimensions of empowering knowledge (bio-physiological, functional, social, experiential, ethical, and financial) on a Likert scale (1=not sufficient at all, 4=very sufficient). Objective sufficiency was evaluated with a structured knowledge test with 10 items (score range 0-10, correct=1, wrong/no knowledge=0) based on the multidimensional content of patient education emphasizing bio-physiological dimension. Results: In subjective sufficiency of knowledge, the mean was 3.27 (SD 0.54). The bio-physiological dimension of empowering knowledge was the most sufficient (mean 3.52, SD 0.49) and the experiential the least (mean 2.8, SD 0.88). In objective sufficiency, the means ranged 5.15-5.97 (SD 2.37-2.68) among patients in different modalities of dialysis care and treatment. The least sufficient objective scores were bio-physiological and functional knowledge. The subjective and objective sufficiency did not correlate with each other. Conclusion: Patients' knowledge, either subjective or objective, does not seem to be sufficient. Hence, attention should be paid to supporting patients with more personalized knowledge. Furthermore, the relationship between subjective and objective sufficiency needs future consideration, as their non-correspondence was a new discovery.Peer reviewe
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