Adenylate Cyclase

Publication Title: 
Aging Cell

?-adrenoceptors are the common pharmacological targets for the treatment of cardiovascular diseases and asthma. Genetic modifications of ?-adrenergic system in engineered mice affect their lifespan. Here, we tested whether genes encoding for key components of the ?-adrenergic signaling pathway are associated with human longevity. We performed a 10-year follow-up study of the Chinese longitudinal healthy longevity survey. The Han Chinese population in this study consisted of 963 long-lived and 1028 geography-matched young individuals.

Author(s): 
Zhao, Ling
Yang, Fan
Xu, Ke
Cao, Huiqing
Zheng, Gu-Yan
Zhang, Yan
Li, Jianxin
Cui, Hanbin
Chen, Xiaomin
Zhu, Zhiming
He, Hongbo
Mo, Xianming
Kennedy, Brian K.
Suh, Yousin
Zeng, Yi
Tian, Xiao-Li
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology

G protein-coupled receptor/adenylyl cyclase (AC)/cAMP signaling is crucial for all cellular responses to physiological and pathophysiological stimuli. There are nine isoforms of membrane-bound AC, with type 5 being one of the two major isoforms in the heart. Since the role of AC in the heart in regulating cAMP and acute changes in inotropic and chronotropic state are well known, this review will address our current understanding of the distinct regulatory role of the AC5 isoform in response to chronic stress.

Author(s): 
Vatner, Stephen F.
Park, Misun
Yan, Lin
Lee, Grace J.
Lai, Lo
Iwatsubo, Kousaku
Ishikawa, Yoshihiro
Pessin, Jeffrey
Vatner, Dorothy E.
Publication Title: 
Aging Cell

Adenylyl cyclase type 5 knockout mice (AC5 KO) live longer and are stress resistant, similar to calorie restriction (CR). AC5 KO mice eat more, but actually weigh less and accumulate less fat compared with WT mice. CR applied to AC5 KO results in rapid decrease in body weight, metabolic deterioration, and death. These data suggest that despite restricted food intake in CR, but augmented food intake in AC5 KO, the two models affect longevity and metabolism similarly.

Author(s): 
Yan, Lin
Park, Ji Yeon
Dillinger, Jean-Guillaume
De Lorenzo, Mariana S.
Yuan, Chujun
Lai, Lo
Wang, Chunbo
Ho, David
Tian, Bin
Stanley, William C.
Auwerx, Johan
Vatner, Dorothy E.
Vatner, Stephen F.
Publication Title: 
Aging
Author(s): 
Vatner, Stephen F.
Vatner, Dorothy E.
Yan, Lin
Publication Title: 
Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan

The chemical constituents of medicinal plants which have been used in Ayurvedic and Tibetan system of medicines in Nepal were examined. From 21 species consisting of 13 genera of the plants, 121 new compounds, whose structures are shown in Charts (1 to 13), were isolated mainly in our laboratory. Some of the compounds and their related ones showed several biological activities.

Author(s): 
Tomimori, T.
Publication Title: 
Arteriosclerosis, Thrombosis, and Vascular Biology

OBJECTIVE: C-Reactive protein (CRP), a cardiovascular risk marker, could also participate in atherosclerosis. Atherosclerotic plaques express CRP and interleukin (IL)-10, a major antiinflammatory cytokine. IL-10 deficiency results in increased lesion formation, whereas IL-10 delivery attenuates lesions. We tested the effect of CRP on lipopolysaccharide (LPS)-induced IL-10 secretion in human monocyte-derived macrophages (HMDMs).

Author(s): 
Singh, Uma
Devaraj, Sridevi
Dasu, Mohan R.
Ciobanu, Dana
Reusch, Jane
Jialal, Ishwarlal
Publication Title: 
The Journal of Nutritional Biochemistry

Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and anti-inflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R-LA and S-LA) stimulates cAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells.

Author(s): 
Salinthone, Sonemany
Schillace, Robynn V.
Tsang, Catherine
Regan, John W.
Bourdette, Dennis N.
Carr, Daniel W.
Publication Title: 
PloS One

BACKGROUND: Lanthionine synthetase component C-like protein 2 (LANCL2) is a member of the eukaryotic lanthionine synthetase component C-Like protein family involved in signal transduction and insulin sensitization. Recently, LANCL2 is a target for the binding and signaling of abscisic acid (ABA), a plant hormone with anti-diabetic and anti-inflammatory effects. METHODOLOGY/PRINCIPAL FINDINGS: The goal of this study was to determine the role of LANCL2 as a potential therapeutic target for developing novel drugs and nutraceuticals against inflammatory diseases.

Author(s): 
Lu, Pinyi
Hontecillas, Raquel
Horne, William T.
Carbo, Adria
Viladomiu, Monica
Pedragosa, Mireia
Bevan, David R.
Lewis, Stephanie N.
Bassaganya-Riera, Josep
Publication Title: 
Cell

Mammalian models of longevity are related primarily to caloric restriction and alterations in metabolism. We examined mice in which type 5 adenylyl cyclase (AC5) is knocked out (AC5 KO) and which are resistant to cardiac stress and have increased median lifespan of approximately 30%. AC5 KO mice are protected from reduced bone density and susceptibility to fractures of aging. Old AC5 KO mice are also protected from aging-induced cardiomyopathy, e.g., hypertrophy, apoptosis, fibrosis, and reduced cardiac function.

Author(s): 
Yan, Lin
Vatner, Dorothy E.
O'Connor, J. Patrick
Ivessa, Andreas
Ge, Hui
Chen, Wei
Hirotani, Shinichi
Ishikawa, Yoshihiro
Sadoshima, Junichi
Vatner, Stephen F.
Publication Title: 
Biological & Pharmaceutical Bulletin

The present study investigated the effect of ferulic acid, a compound purified from traditional Chinese herbal medicine Chuanxiong and Awei, on anion secretion by human colonic cells (T84) using the short circuit current (I(SC)) and microspectrofluorimetric technique. Basolateral administration of sodium ferulate (SF) produced a concentration-dependent increase of I(SC) in T84 cells with an EC50 of 1.2 mM. The SF-induced increase in I(SC) contained a transient peak followed by a sustained plateau.

Author(s): 
Zhao, Wen Chao
Zhu, Jin Xia
Zhang, Gui Hong
Wong, Connie Hau Yan
Chung, Yiu Wa
Chan, Hsiao Chang
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