• Animal cells and systems
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• 제9권3호
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• pp.173-179
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• 2005

Cyclic-AMP-dependent protein kinase (PKA) seems to function as a negative regulator of the c-Jun $NH_2-terminal$ kinase (JNK) signaling pathway. We demonstrate here that the activity of the PKA catalytic subunit (PKAc) is reduced in apoptotic PC12 pheochromocytoma cells. Apoptotic progress was inhibited by dibutyryl cyclic AMP (dbcAMP), an analog of cAMP. The rescue by dbcAMP was attributable to inhibition of the JNK but not of the p38 signaling pathway, due to the induction of PKA activity. JNK was present in immunocomplexes of PKAc, and PKAc phosphorylated JNK in vitro. Presence of p38 kinase, however, was not prominent in immunocomplexes of PKAc. Our data suggest that JNK is a target point of negative regulation by PKAc in the JNK signaling pathway.

• Journal of Microbiology and Biotechnology
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• 제15권3호
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• pp.665-671
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• 2005

Initiation and activation of sperm motility are prerequisite processes for the contact and fusion of male and female gametes at fertilization. The phenomena are under the regulation of cAMP and $Ca^{2+}$ in vertebrates and invertebrates. Mammalian sperm requires $Ca^{2+}$ and cAMP for the activation of sperm motility. Cell signaling for the initiation and activation of sperm motility in the ascidians and salmonid fishes has drawn much attention. In the ascidians, the sperm-activating and attracting factors from unfertilized egg require extracellular $Ca^{2+}$ for activating sperm motility and eliciting chemotactic behavior toward the egg. On the other hand, the cAMP-dependent phosphorylation of protein is essential for the initiation of sperm motility in salmonid fishes. A decrease of the environmental $K^+$ concentration surrounding the spawned sperm causes $K^+$ efflux and $Ca^{2+}$ influx through the specific $K^+$ channel and dihydropyridine-sensitive L-/T-type $Ca^{2+}$ channel, respectively, thereby leading to the membrane hyperpolarization. The membrane hyperpolarization induces synthesis of cAMP, which triggers further cell signaling processes, such as cAMP-dependent protein phosphorylation, to initiate sperm motility in salmonid fishes. This article reviews the studies on the physiological mechanisms of sperm motility and its cell signaling in aquatic species.

• Mycobiology
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• 제38권1호
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• pp.26-32
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• 2010

The cyclic AMP (cAMP) pathway plays a major role in growth, sexual differentiation, and virulence factor synthesis of pathogenic fungi. In Cryptococcus neoformans, perturbation of the cAMP pathway, such as a deletion in the gene encoding adenylyl cyclase (CAC1), causes defects in the production of virulence factors, including capsule and melanin production, as well as mating. Previously, we performed a comparative transcriptome analysis of the Ras- and cAMP- pathway mutants, which revealed 163 potential cAMP-regulated genes (38 genes at a 2-fold cutoff). The present study characterized the role of one of the cAMP pathway-dependent genes (serotype A identification number CNAG_ 06576.2). The expression patterns were confirmed by Northern blot analysis and the gene was designated cAMP-regulated gene 1 (CAR1). Interestingly, deletion of CAR1 did not affect biosynthesis of any virulence factors and the mating process, unlike the cAMP-signaling deficient cac1$\Delta$ mutant. Furthermore, the car1$\Delta$ mutant exhibited wild-type levels of the stress-response phenotype against diverse environmental cues, indicating that Car1, albeit regulated by the cAMP-pathway, is not essential to confer a cAMP-dependent phenotype in C. neoformans.

• 한국발생생물학회지:발생과생식
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• 제7권2호
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• pp.81-88
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• 2003

정자의 운동개시는 수정시에 정자와 난자가 만나기 위한 전제조건이다. 동물의 정자는 CAMP와Ca2'의 조절기구에 의해서 정자의 운동개시가 일어난다. 정자운동 활성 및 개시를 위한 세포 신호전달기구는 멍게류와 연어과 어류에서 많은 연구가 이루어져 왔다. 멍게류의 경우, 난에서 분비되는 정자 활성 및 유인물질(sperm-activating and -attracting factor)은 정자 활성 및 난으로의 유인을 위하여 외부의 $Ca^{2+}$을 요구한다. 한편 연어과 어류의 정자에서는 Cyclic AMP 의존형의 단백질 인산화가 정자 운동개시 기구에 관여한다. 방정된 정자 주위의 $K^{+}$ 농도의 감소는 특정한 $K^{+}$ channel 및 dihydropyridine 감수성의 L-/T- type $Ca^{2+}$ channel을 통한 $K^{+}$ 유출과 $Ca^{2+}$ 유입에 의해 세포막의 과분극과 세포내 $Ca^{2+}$ 이온의 농도증가를 가져온다. 세포막의 과분극에 의해서 합성된 cyclic AMP는 정자 운동개시의 주요기구인 cyclic AMP의존형의 단백질 인산화를 유도한다.

• 대한의생명과학회지
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• 제27권4호
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• pp.270-276
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• 2021

Physiological agents trigger a signaling process called "inside-out signaling" and activated platelets promote adhesion, granule release, and conformational changes of glycoprotein IIb/IIIa (αIIb/β₃). Activated αIIb/β₃ interacts with fibrinogen and initiates a second signaling step called "external signaling". These two signaling pathways can cause hemostasis or thrombosis, and thrombosis is a possible medical problem in arterial and venous vessels, and platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, modulating platelet activity is important for platelet-mediated thrombosis and cardiovascular disease. Esculetin is a coumarin-based physiologically active 6,7-dihydroxy derivative known to have pharmacological activity against obesity, diabetes, renal failure and CVD. Although some studies have confirmed the effects of esculetin in human platelet activation and experimental mouse models, it is not clear how esculetin has antiplatelet and antithrombotic effects. We confirmed the effect and mechanism of action of escultein on human platelets induced by collagen. As a result, esculetin decreased Ca²⁺ recruitment through upregulation of inositol 1, 4, 5-triphosphate receptor. In addition, esculetin upregulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-dependent pathways and inhibits fibrinogen binding and thrombus contraction. Our results demonstrate the antiplatelet effect and antithrombotic effect of esculetin in human platelets. Therefore, we suggest that esculetin could be a potential phytochemical for the prevention of thrombus-mediated CVD.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.203-210
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• 2015

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

• Journal of Microbiology and Biotechnology
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• 제17권7호
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• pp.1198-1203
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• 2007

Conidial adhesion and appressorium formation of Magnaporthe oryzae on the rice surface are important early events in the infection process. As an initiative step to understand the mechanisms underlying these cellular processes at a biochemical level, the effect of a human fibronectin antibody (HFA) and RGD peptides on conidial adhesion and appressorium formation was evaluated. HFA inhibited conidial adhesion and appressorium formation in a dosage-dependent manner. RGD peptides also inhibited these cellular events. Conidial adhesion and appressorium formation inhibited by RGD peptides were restored by chemicals involved in the cyclic AMP-dependent signaling pathway. These results suggest that extracellular matrix proteins might be involved in conidial adhesion and appressorium formation through integrin-like receptor mediation and modulation of cAMP-dependent signaling in the cells.

• BMB Reports
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• 제45권12호
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• pp.724-729
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• 2012

In this study, we evaluated the anti-melanogenesis effects of Caffeoylserotonin (CaS) in B16 melanoma cells. Treatment with CaS reduced the melanin content and tyrosinase (TYR) activity in B16 melanoma cells in a dose-dependent manner. CaS inhibited the expression of melanogenesis-related proteins, including microphthalmia-associated transcription factor (MITF), TYR, and tyrosinase-related protein-1 (TRP-1), but not TRP-2. ${\alpha}$-MSH is known to interact with melanocortin 1 receptor (MC1R) thus activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP) levels. Furthermore, cAMP activates extracellular signal-regulated kinase 2 (ERK2) via phosphorylation, which phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphorylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on ${\alpha}$-MSH-induced melanogenesis. Based on this study, the inhibitory effects of CaS on melanogenesis are derived from the downregulation of MITF signaling via the inhibition of intracellular cAMP levels, as well as acceleration of ERK activation.

• BMB Reports
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• 제44권3호
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• pp.205-210
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• 2011

Insulin has antiapoptotic activity in various cell types. However, the signaling pathways underlying the antiapoptotic activity of insulin is not yet known. This study was conducted to determine if cAMP affects the antiapoptotic activity of insulin and the activity of PI3K and ERK in CHO cells expressing human insulin receptors (CHO-IR). Insulin-stimulated ERK activity was completely suppressed by cAMP-elevating agents like as pertussis toxin (Ptx) and cholera toxin (Ctx) after 4 h treatment. Insulin-stimulated PKB/Akt activity was not affected at all. Ptx treatment together with insulin increased the number of apoptotic cells and the degree of DNA fragmentation. Ctx or 8-br-cAMP treatment also increased the number of apoptotic cells and stimulated the cleavage of caspase-3 and the hydrolysis of PARP. Taken together, cAMP antagonizes the antiapoptotic activity of insulin and the main target molecule of cAMP in this process is likely ERK, not PI3K-dependent PKB/Akt.

• The Korean Journal of Physiology and Pharmacology
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• 제6권3호
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• pp.139-142
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• 2002

To examine intracellular signaling of human $S1P_3\;(hS1P_3),$ a sphingosine 1-phosphate (S1P) receptor in plasma membrane, $hS1P_3$ DNA was transfected into RH7777 rat hepatoma cell line, and the inhibition of forskolin-induced cAMP accumulation and activation of MAP kinases by S1P were tested. In $hS1P_3$ transformants, S1P inhibited forskolin-induced activation of adenylyl cyclase activity by about 80% and activated MAP kinases in dose-dependent and pertussis-toxin (PTX) sensitive manners. In oocytes expressing $hS1P_3$ receptor, S1P evoked $Cl^-$ conductance. These data suggested that PTX-sensitive G proteins are involved in $hS1P_3-mediated$ signaling, especially the positive action of S1P in cell proliferation. The potential advantages of rat hepatoma cells for the research of sphingosine 1-phosphate receptor are discussed.