scholarly journals Inhibition of p66ShcA redox activity in cardiac muscle cells attenuates hyperglycemia-induced oxidative stress and apoptosis

2009 ◽  
Vol 296 (2) ◽  
pp. H380-H388 ◽  
Author(s):  
Ashwani Malhotra ◽  
Himanshu Vashistha ◽  
Virendra S. Yadav ◽  
Michael G. Dube ◽  
Satya P. Kalra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Cardiac Muscle ◽  
Ventricular Myocytes ◽  
Muscle Cells ◽  
Molecular Switch ◽  
Left Ventricular ◽  
Cardiac Muscle Cells ◽  
Rat Ventricular Myocytes ◽  
Adult Rat

Apoptotic myocyte cell death, diastolic dysfunction, and progressive deterioration in left ventricular pump function characterize the clinical course of diabetic cardiomyopathy. A key question concerns the mechanism(s) by which hyperglycemia (HG) transmits danger signals in cardiac muscle cells. The growth factor adapter protein p66ShcA is a genetic determinant of longevity, which controls mitochondrial metabolism and cellular responses to oxidative stress. Here we demonstrate that interventions which attenuate or prevent HG-induced phosphorylation at critical position 36 Ser residue (phospho-Ser36) inhibit the redox function of p66ShcA and promote the survival phenotype. Adult rat ventricular myocytes obtained by enzymatic dissociation were transduced with mutant-36 p66ShcA (mu-36) dominant-negative expression vector and plated in serum-free media containing 5 or 25 mM glucose. At HG, adult rat ventricular myocytes exhibit a marked increase in reactive oxygen species production, upregulation of phospho-Ser36, collapse of mitochondrial transmembrane potential, and increased formation of p66ShcA/cytochrome- c complexes. These indexes of oxidative stress were accompanied by a 40% increase in apoptosis and the upregulation of cleaved caspase-3 and the apoptosis-related proteins p53 and Bax. To test whether p66ShcA functions as a redox-sensitive molecular switch in vivo, we examined the hearts of male Akita diabetic nonobese (C57BL/6J) mice. Western blot analysis detected the upregulation of phospho-Ser36, the translocation of p66ShcA to mitochondria, and the formation of p66ShcA/cytochrome- c complexes. Conversely, the correction of HG by recombinant adeno-associated viral delivery of leptin reversed these alterations. We conclude that p66ShcA is a molecular switch whose redox function is turned on by phospho-Ser36 and turned off by interventions that prevent this modification.

Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT1 receptors

2002 ◽  
Vol 283 (2) ◽  
pp. H461-H467 ◽  
Author(s):  
Hai Ling Li ◽  
Jun Suzuki ◽  
Evelyn Bayna ◽  
Fu-Min Zhang ◽  
Erminia Dalle Molle ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ventricular Myocytes ◽  
Annexin V ◽  
Left Ventricular ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Cardiac Apoptosis

Lipopolysaccharide (LPS) from gram-negative bacteria circulates in acute, subacute, and chronic conditions. It was hypothesized that LPS directly induces cardiac apoptosis. In adult rat ventricular myocytes (isolated with depyrogenated digestive enzymes to minimize tolerance), LPS (10 ng/ml) decreased the ratio of Bcl-2 to Bax at 12 h; increased caspase-3 activity at 16 h; and increased annexin V, propidium iodide, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining at 24 h. Apoptosis was blocked by the caspase inhibitor benzyloxycarbonyl-valine-alanine-aspartate fluoromethylketone (Z-VAD-fmk), captopril, and angiotensin II type 1 receptor (AT1) inhibitor (losartan), but not by inhibitors of AT2 receptors (PD-123319), tumor necrosis factor-α (TNFRII:Fc), or nitric oxide ( N G-monomethyl-l-arginine). Angiotensin II (100 nmol/l) induced apoptosis similar to LPS without additive effects. LPS in vivo (1 mg/kg iv) increased apoptosis in left ventricular myocytes for 1–3 days, which dissipated after 1–2 wk. Losartan (23 mg · kg−1 · day−1 in drinking water for 3 days) blocked LPS-induced in vivo apoptosis. In conclusion, low levels of LPS induce cardiac apoptosis in vitro and in vivo by activating AT1 receptors in myocytes.

Lipid Droplet Accumulation in Cardiac Muscle Cells of the Bat: Induction by Reserpine and Antagonism by Atropine

1975 ◽  
Vol 33 ◽  
pp. 534-535
Author(s):  
Martin Hagopian ◽  
Eladio A. Nunez ◽  
Michael D. Gershon
Keyword(s):  
Cardiac Muscle ◽  
Lipid Droplets ◽  
Single Injection ◽  
Sympathetic Innervation ◽  
Muscle Cells ◽  
Left Ventricular ◽  
High Dose ◽  
Cardiac Muscle Cells ◽  
Cardiac Sympathetic Innervation ◽  
Point Count

Reserpine has been shown to induce the accumulation of large numbers of lipid inclusions in cardiac muscle cells of the bat. This effect of reserpine is seen 24 hours after a single injection of 5 mg/kg of the drug. Since the action of reserpine can be antagonized by chemical sympathectomy with 6-hydroxydopamine and mimicked by norepinephrine, we have postulated the involvement of the cardiac sympathetic innervation in mediating reserpine's effect. In the present investigation we have examined the ability of atropine to prevent the accumulation of lipid droplets in cardiac muscle after a single injection of reserpine. Two dose schedules of atropine were tried. A high dose consisted of 3 injections, 9 mg/kg each, given intraperitoneally at 8 hour intervals beginning one hour prior to challenge with reserpine. A low dose consisted of 2 mg/kg given the same way. Left ventricular muscle was examined by electron microscopy and the relative cardiocyte volume occupied by lipid droplets was quantitated from electron micrographs by point count planimetry.

Effects of hypoxia on cardiac growth in neonatal rat

1976 ◽  
Vol 231 (5) ◽  
pp. 1445-1450 ◽  
Author(s):  
M Hollenberg ◽  
N Honbo ◽  
AJ Samorodin
Keyword(s):  
Body Weight ◽  
Left Ventricle ◽  
Cardiac Muscle ◽  
Neonatal Period ◽  
Vascular Endothelial Cells ◽  
Muscle Cells ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Low Oxygen ◽  
Cardiac Muscle Cells

To determine whether low oxygen environments enhance cardiac cell division in the neonatal period, newborn rat pups were reared for 21 days in 12-15% oxygen. Left ventricle and right ventricle weights were 30 and 180% greater than controls matched for body weight (P less than 0.001) as were left ventricle/body weight ratios (3.68+/-0.26 vs. 2.99+/-0.05 mg LV/g body wt,P less than 0.001). Left ventricular total DNA and DNA concentration was 95 and 48% greater than controls (P less than 0.001). Autoradiography confirmed that this increase in ventricular DNA resulted from an increased rate of division of cardiac muscle cells, fibroblast, and vascular endothelial cells. When [3H]thymidine was injected on day ), autoradiographs prepared on day 21 reflected an increased dilution of label in hypoxic rats consistent with enhanced proliferation. The labeling index and grains per nucleus of ventricular muscle cells was 25% (P less than 0.01) and 20% (P less than 0.02) less than controls, Thus, hypoxic stress applied early in the neonatal period augments the rate of division and ultimate number of cardiac muscle cells. Whether this enhancement results from a primary effect of oxygen or from secondary hemodynamic factors remains unknown.

scholarly journals Metabolites of MDMA Induce Oxidative Stress and Contractile Dysfunction in Adult Rat Left Ventricular Myocytes

2009 ◽  
Vol 9 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Sylvia K. Shenouda ◽  
Kurt J. Varner ◽  
Felix Carvalho ◽  
Pamela A. Lucchesi
Keyword(s):  
Oxidative Stress ◽  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Adult Rat

Fine Structure of Cardiac Muscle Cells after Injection of Normal and Thiouracil-Treated Rats with Triiodothyronine.

1975 ◽  
Vol 33 ◽  
pp. 536-537
Author(s):  
Eladio A. Nunez ◽  
Martin Hagopian ◽  
Roger L. Greif ◽  
Michael D. Gershon
Keyword(s):  
Drinking Water ◽  
Fine Structure ◽  
Thyroid Hormones ◽  
Cardiac Muscle ◽  
Muscle Cells ◽  
Left Ventricular ◽  
Ventricular Muscle ◽  
Cardiac Muscle Cells ◽  
Mitochondrial Number ◽  
Morphologic Changes

It has been reported that morphologic changes occur in mitochondria of cardiac muscle cells following treatment with thyroid hormones (thyroxine, triiodothyronine). These observations have been used to support the view that under normal conditions, thyroid hormones control mitochondrial metabolism. We have examined the effect of triiodothyronine on the fine structure of cardiac muscle from normal and thiouracil-treated rats. Rats were given thiouracil (0.1 percent in drinking water) for 10 weeks. Normal and thiouracil-treated rats were injected with triiodothyronine (75 ug of triiodo-L-thyronine i.p. per day) for three days. The left ventricular muscle of normal rats, and rats given thiouracil, triiodothyronine or thiouracil followed by triiodothyronine was examined ultrastructurally. Morphometric analysis of electron micrographs showed that mitochondrial number was not significantly different in the four groups of animals. The fine structure of normal cardiac muscle is illustrated in figure 1. Thiouracil treatment did not alter the fine structure of cardiac muscle cells (Fig. 3).

scholarly journals Proliferating cell nuclear antigen in developing and adult rat cardiac muscle cells.

1991 ◽  
Vol 69 (5) ◽  
pp. 1353-1360 ◽  
Author(s):  
T A Marino ◽  
S Haldar ◽  
E C Williamson ◽  
K Beaverson ◽  
R A Walter ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Proliferating Cell Nuclear Antigen ◽  
Muscle Cells ◽  
Nuclear Antigen ◽  
Cardiac Muscle Cells ◽  
Adult Rat ◽  
Proliferating Cell
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