Stretch-Induced Map Kinase Activation in Cardiomyocytes of Angiotensinogen-Deficient Mice

Nyui, Nobuo; Tamura, Kouichi; Mizuno, Keiko; Ishigami, Tomoaki; Hibi, Kiyoshi; Yabana, Machiko; Kihara, Minoru; Fukamizu, Akiyoshi; Ochiai, Hisao; Umemura, Satoshi; Murakami, Kazuo; Ohno, Shigeo; Ishii, Masao

doi:10.1006/bbrc.1997.6706

Cited by 36 publications

(17 citation statements)

References 23 publications

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“…Myocyte Preparation-Primary cultures of neonatal mouse cardiomyocytes were prepared from the heart of a 1-day-old mouse, as described previously with some modifications (24). Briefly, trypsinization and collagenization were performed, and cardiomyocytes were maintained at 37°C in humidified air with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Direct Inhibition of Type 5 Adenylyl Cyclase Prevents Myocardial Apoptosis without Functional Deterioration

Iwatsubo

Minamisawa

Takemoto

et al. 2004

Journal of Biological Chemistry

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101

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Adenylyl cyclase, a major target enzyme of ␤-adrenergic receptor signals, is potently and directly inhibited by P-site inhibitors, classic inhibitors of this enzyme, when the enzyme catalytic activity is high. Unlike ␤-adrenergic receptor antagonists, this is a non-or uncompetitive inhibition with respect to ATP. We have examined whether we can utilize this enzymatic property to regulate the effects of ␤-adrenergic receptor stimulation differentially. After screening multiple new and classic compounds, we found that some compounds, including 1R,4R-3-(6-aminopurin-9-yl)-cyclopentanecarboxylic acid hydroxyamide, potently inhibited type 5 adenylyl cyclase, the major cardiac isoform, but not other isoforms. In normal mouse cardiac myocytes, contraction induced by low ␤-adrenergic receptor stimulation was poorly inhibited with this compound, but the induction of cardiac myocyte apoptosis by high ␤-adrenergic receptor stimulation was effectively prevented by type 5 adenylyl cyclase inhibitors. In contrast, when cardiac myocytes from type 5 adenylyl cyclase knock-out mice were examined, ␤-adrenergic stimulation poorly induced apoptosis. Our data suggest that the inhibition of ␤-adrenergic signaling at the level of the type 5 adenylyl cyclase isoform by P-site inhibitors may serve as an effective method to prevent cardiac myocyte apoptosis induced by excessive ␤-adrenergic stimulation without deleterious effect on cardiac myocyte contraction.Adrenergic stimulation via the sympathetic nervous system is a major mechanism to regulate cardiac function (1). Norepinephrine released from the synaptic terminal binds to ␤-adrenergic receptors (␤-AR), 1 leading to the activation of adenylyl cyclase (AC) and thus the production of cAMP, which initiates a cascade of protein phosphorylation and regulation of many key signaling elements involved in muscle contraction and calcium handling. The immediate outcome of this stimulation is increased cardiac contractility and output. Pharmacological inhibition of this pathway, by the use of ␤-AR antagonists, has been widely utilized to attenuate cardiac function in the clinical setting of treating high blood pressure for several decades. Recently, ␤-AR antagonists have been used in the treatment of heart failure, i.e. in hearts with deteriorated cardiac function. This paradoxical usage of ␤-AR antagonists in heart failure has been rationalized by the protection of the heart from excessive sympathetic stimulation. Under this pathological condition, it is well known that the sympathetic activity is increased markedly (2-4), leading to the remodeling of the heart (5) and, more importantly, the induction of cardiac myocyte apoptosis, as demonstrated by both in vivo and in vitro studies (6, 7). However, a major problem in introducing ␤-AR antagonist therapy is the worsening of cardiac function (8).It is believed that regulating ␤-adrenergic signaling at the level of AC, instead of the receptor, may serve as an alternative to the common ␤-AR regulating therapy, which is most exemplified by direct ...

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Section: Methodsmentioning

confidence: 99%

Direct Inhibition of Type 5 Adenylyl Cyclase Prevents Myocardial Apoptosis without Functional Deterioration

Iwatsubo

Minamisawa

Takemoto

et al. 2004

Journal of Biological Chemistry

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101

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“…Western blot analysis was performed essentially as described in a previous study (24). Protein was isolated from VSMCs using buffers and protease inhibitors (50 mmol/l Tris-HCl pH 8.0, 2 mmol/l ethyleneglycol bis (2-aminoethyl-ether) tetraacetic acid (EGTA), 10 µmol/l phenylmethylsulfonyl fluoride (PMSF), 10 µg/ml leupeptin, 1.25 mg/ml trypsin inhibitor from chicken egg white (ETI) and 1% SDS).…”

Section: Western Blot Analysismentioning

confidence: 99%

Lipoxygenase Products Regulate Nitric Oxide and Inducible Nitric Oxide Synthase Production in Interleukin-1.BETA. Stimulated Vascular Smooth Muscle Cells.

Hashimoto¹,

Kihara²,

Yokoyama³

et al. 2003

Hypertens Res

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“…Another important consequence of taurine-induced cell volume regulation is the modulation of the stretch-dependent, angiotensin IIindependent receptor (Kent and McDermott, 1996;Nyui et al, 1997;Thienault et al, 1997). The signaling cascade activated by this stretch receptor includes the activation of a phospholipase that promotes the accumulation of inositol phosphates and the translocation of PKC-epsilon (Paul et al, 1997).…”

Section: Effect Of Taurine On Angiotensin II Signaling Pathwaymentioning

confidence: 99%

Interaction between the actions of taurine and angiotensin II

2000

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The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion of taurine has been linked to developmental defects, retinal damage, immunodeficiency, impaired cellular growth and the development of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy promoting drinks. Nonetheless, the use of taurine as a drug to treat specific diseases has been limited. One disease that responds favorably to taurine therapy is congestive heart failure. In this review, we discuss three mechanisms that might underlie the beneficial effect of taurine in heart failure. First, taurine promotes natriuresis and diuresis, presumably through its osmoregulatory activity in the kidney, its modulation of atrial natriuretic factor secretion and its putative regulation of vasopressin release. However, it remains to be determined whether taurine treatment promotes salt and water excretion in humans with heart failure. Second, taurine mediates a modest positive inotropic effect by regulating [Na+]i and Na+/Ca2+ exchanger flux. Although this effect of taurine has not been examined in human tissue, it is significant that it bypasses the major calcium transport defects found in the failing human heart. Third, taurine attenuates the actions of angiotensin II on Ca2+ transport, protein synthesis and angiotensin II signaling. Through this mechanism taurine would be expected to minimize many of the adverse actions of angiotensin II, including the induction of cardiac hypertrophy, volume overload and myocardial remodeling. Since the ACE inhibitors are the mainstay in the treatment of congestive heart failure, this action of taurine is probably very important.

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Stretch-Induced Map Kinase Activation in Cardiomyocytes of Angiotensinogen-Deficient Mice

Cited by 36 publications

References 23 publications

Direct Inhibition of Type 5 Adenylyl Cyclase Prevents Myocardial Apoptosis without Functional Deterioration

Direct Inhibition of Type 5 Adenylyl Cyclase Prevents Myocardial Apoptosis without Functional Deterioration

Lipoxygenase Products Regulate Nitric Oxide and Inducible Nitric Oxide Synthase Production in Interleukin-1.BETA. Stimulated Vascular Smooth Muscle Cells.

Interaction between the actions of taurine and angiotensin II

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