Soluble CD14 inhibits contractile function and insulin action in primary adult rat cardiomyocytes

In many types of heart failure cardiac myocyte Ca2+ handling is abnormal because of downregulation of key Ca2+-handling proteins like sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a and ryanodine receptor (RyR)2. The alteration in SERCA2a and RyR2 expression results in altered cytosolic Ca2+ transients, leading to abnormal contraction. Sorcin is an EF-hand protein that confers the property of caffeine-activated intracellular Ca2+ release in nonmuscle cells by interacting with RyR2. To determine whether sorcin could improve the contractile function of the heart, we overexpressed sorcin in the heart of either normal or diabetic mice and in adult rat cardiomyocytes with an adenoviral gene transfer approach. Sorcin overexpression was associated with an increase in cardiac contractility of the normal heart and dramatically rescued the abnormal contractile function of the diabetic heart. These effects could be attributed to an improvement of the Ca2+ transients found in the cardiomyocyte after sorcin overexpression. Viral vector-mediated delivery of sorcin to cardiac myocytes is beneficial, resulting in improved contractile function in diabetic cardiomyopathy.

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Contractile Function is Altered by Regulation of HO-1 Activity in Single Adult Rat Cardiomyocytes

Biophysical Journal ◽

10.1016/j.bpj.2009.12.3943 ◽

2010 ◽

Vol 98 (3) ◽

pp. 720a

Author(s):

Sarah Nowakowski ◽

F. Steven Korte ◽

Jun Luo ◽

Margaret Allen ◽

Michael Regnier

Keyword(s):

Contractile Function ◽

Rat Cardiomyocytes ◽

Adult Rat

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Regulation of myocardial function by histidine-rich, calcium-binding protein

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01211.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. H1705-H1711 ◽

Cited By ~ 45

Author(s):

Guo-Chang Fan ◽

Kimberly N. Gregory ◽

Wen Zhao ◽

Woo Jin Park ◽

Evangelia G. Kranias

Keyword(s):

Heart Failure ◽

Ryanodine Receptor ◽

Calcium Binding ◽

Recombinant Adenovirus ◽

Contractile Function ◽

Binding Protein ◽

Human Heart Failure ◽

Rat Cardiomyocytes ◽

Adult Rat ◽

Protein Levels

Impaired sarcoplasmic reticulum (SR) Ca release has been suggested to contribute to the depressed cardiac function in heart failure. The release of Ca from the SR may be regulated by the ryanodine receptor, triadin, junctin, calsequestrin, and a histidine-rich, Ca-binding protein (HRC). We observed that the levels of HRC were reduced in animal models and human heart failure. To gain insight into the physiological function of HRC, we infected adult rat cardiac myocytes with a recombinant adenovirus that contains the full-length mouse HRC cDNA. Overexpression (1.7-fold) of HRC in adult rat cardiomyocytes was associated with increased SR Ca load (28%) but decreased SR Ca-induced Ca release (37%), resulting in impaired Ca cycling and depressed fractional shortening (36%) as well as depressed rates of shortening (38%) and relengthening (33%). Furthermore, the depressed basal contractile and Ca kinetic parameters in the HRC-infected myocytes remained significantly depressed even after maximal isoproterenol stimulation. Interestingly, HRC overexpresssion was accompanied by increased protein levels of junctin (1.4-fold) and triadin (1.8-fold), whereas the protein levels of ryanodine receptor, calsequestrin, phospholamban, and sarco(endo)plasmic reticulum Ca-ATPase remained unaltered. Collectively, these data indicate that alterations in expression levels of HRC are associated with impaired cardiac SR Ca homeostasis and contractile function.

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Resveratrol prevents palmitic-acid-induced cardiomyocyte contractile impairment

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0051 ◽

2019 ◽

Vol 97 (12) ◽

pp. 1132-1140

Author(s):

Xavier Lieben Louis ◽

Pema Raj ◽

Zach Meikle ◽

Liping Yu ◽

Shannel E. Susser ◽

...

Keyword(s):

Protein Expression ◽

Palmitic Acid ◽

Troponin I ◽

Contractile Function ◽

Morphological Changes ◽

Saturated Fatty Acids ◽

Rat Cardiomyocytes ◽

Adult Rat ◽

Pre Treatment ◽

Hoechst Staining

Long-chain saturated fatty acids, especially palmitic acid (PA), contribute to cardiomyocyte lipotoxicity. This study tests the effects of PA on adult rat cardiomyocyte contractile function and proteins associated with calcium regulating cardiomyocyte contraction and relaxation. Adult rat cardiomyocytes were pretreated with resveratrol (Resv) and then treated with PA. For the reversal study, cardiomyocytes were incubated with PA prior to treatment with Resv. Cardiomyocyte contractility, ratio of rod- to round-shaped cardiomyocytes, and Hoechst staining were used to measure functional and morphological changes in cardiomyocytes. Protein expression of sarco-endoplasmic reticulum ATPase 2a (SERCA2a), native phospholamban (PLB) and phosphorylated PLB (pPLB ser16 and pPLB thr17), and troponin I (TnI) and phosphorylated TnI (pTnI) were measured. SERCA2a activity was also measured. Our results show that PA (200 μM) decreased the rate of cardiomyocyte relaxation, reduced the number of rod-shaped cardiomyocytes, and increased the number of cells with condensed nuclei; pre-treating cardiomyocytes with Resv significantly prevented these changes. Post-treatment with Resv did not reverse morphological changes induced by PA. Protein expression levels of SERCA2a, PLB, pPLBs, TnI, and pTnI were unchanged by PA or Resv. SERCA2a activity assay showed that Vmax and Iono ratio were increased with PA and pre-treatment with Resv prevented this increase. In conclusion, our results show that Resv protect cardiomyocytes from contractile dysfunction induced by PA.

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Urotensin II and Urocortin promote adult rat cardiomyocytes hypertrophy together with phosphorylation of the Protein Kinase B- Glycogen Synthase Kinase 3b pathway and stabilization of b-catenin

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(08)60324-0 ◽

2008 ◽

Vol 7 ◽

pp. 117-117

Author(s):

D GRUSON ◽

L BERTRAND ◽

A GINION ◽

N DECROLY ◽

V DECONINCK ◽

...

Keyword(s):

Protein Kinase ◽

Glycogen Synthase ◽

Protein Kinase B ◽

Glycogen Synthase Kinase ◽

Urotensin Ii ◽

Rat Cardiomyocytes ◽

Adult Rat

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The adiponectin paralog CTRP9 but not CTRP7 mediates anti-oxidative effects in adult rat cardiomyocytes through an AMPK, adiponectin receptor and calreticulin dependent mechanism

Diabetologie und Stoffwechsel ◽

10.1055/s-0035-1549595 ◽

2015 ◽

Vol 10 (S 01) ◽

Author(s):

L Li ◽

D Stumpp ◽

B Siegler ◽

M Micoogullari ◽

B Niemann ◽

...

Keyword(s):

Adiponectin Receptor ◽

Rat Cardiomyocytes ◽

Adult Rat ◽

Oxidative Effects ◽

Dependent Mechanism

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IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

Cell Death Discovery ◽

10.1038/s41420-021-00404-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Guixi Mo ◽

Xin Liu ◽

Yiyue Zhong ◽

Jian Mo ◽

Zhiyi Li ◽

...

Keyword(s):

Myocardial Ischemia ◽

Ischemia Reperfusion Injury ◽

Cell Model ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

Rat Cardiomyocytes ◽

Adult Rat ◽

Caspase 1 ◽

Intracellular Ca ◽

Myocardial Ischemia Reperfusion

AbstractIntracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.

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