scholarly journals Physiological role of ROCKs in the cardiovascular system

2006 ◽  
Vol 290 (3) ◽  
pp. C661-C668 ◽  
Author(s):  
Kensuke Noma ◽  
Naotsugu Oyama ◽  
James K. Liao
Keyword(s):  
Protein Kinase ◽  
Cardiovascular System ◽  
Vascular Inflammation ◽  
Physiological Role ◽  
Smooth Muscle Contraction ◽  
Kinase Substrate ◽  
Cytoskeleton Organization ◽  
Beneficial Effects ◽  
Actin Cytoskeleton Organization

Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

scholarly journals Characterization of the Role of AMP-Activated Protein Kinase in the Regulation of Glucose-Activated Gene Expression Using Constitutively Active and Dominant Negative Forms of the Kinase

2000 ◽  
Vol 20 (18) ◽  
pp. 6704-6711 ◽  
Author(s):  
Angela Woods ◽  
Dalila Azzout-Marniche ◽  
Marc Foretz ◽  
Silvie C. Stein ◽  
Patricia Lemarchand ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Fatty Acid Synthase ◽  
Physiological Role ◽  
Rat Hepatocytes ◽  
Dominant Negative ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Constitutively Active

ABSTRACT In the liver, glucose induces the expression of a number of genes involved in glucose and lipid metabolism, e.g., those encoding L-type pyruvate kinase and fatty acid synthase. Recent evidence has indicated a role for the AMP-activated protein kinase (AMPK) in the inhibition of glucose-activated gene expression in hepatocytes. It remains unclear, however, whether AMPK is involved in the glucose induction of these genes. In order to study further the role of AMPK in regulating gene expression, we have generated two mutant forms of AMPK. One of these (α1312) acts as a constitutively active kinase, while the other (α1DN) acts as a dominant negative inhibitor of endogenous AMPK. We have used adenovirus-mediated gene transfer to express these mutants in primary rat hepatocytes in culture in order to determine their effect on AMPK activity and the transcription of glucose-activated genes. Expression of α1312 increased AMPK activity in hepatocytes and blocked completely the induction of a number of glucose-activated genes in response to 25 mM glucose. This effect is similar to that observed following activation of AMPK by 5-amino-imidazolecarboxamide riboside. Expression of α1DN markedly inhibited both basal and stimulated activity of endogenous AMPK but had no effect on the transcription of glucose-activated genes. Our results suggest that AMPK is involved in the inhibition of glucose-activated gene expression but not in the induction pathway. This study demonstrates that the two mutants we have described will provide valuable tools for studying the wider physiological role of AMPK.

scholarly journals Modulation of Actin network and Tau phosphorylation by HDAC6 ZnF UBP domain

2019 ◽  
Author(s):  
Abhishek Ankur Balmik ◽  
Shweta Kishor Sonawane ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Nuclear Localization ◽  
Tau Phosphorylation ◽  
Actin Network ◽  
Cytoskeletal Organization ◽  
Protein Tau ◽  
Cytoskeleton Organization ◽  
Actin Cytoskeleton Organization ◽  
Aggresome Formation ◽  
Gsk 3Β

AbstractMicrotubule-associated protein Tau undergoes aggregation in Alzheimer’s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits polyubiquitinated aggregates to the motor protein dynein. Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemistry. Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre. Our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases.

scholarly journals Effects and Mechanisms of Tea Regulating Blood Pressure: Evidences and Promises

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1115 ◽  
Author(s):  
Daxiang Li ◽  
Ruru Wang ◽  
Jinbao Huang ◽  
Qingshuang Cai ◽  
Chung S. Yang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Animal Studies ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Vascular Inflammation ◽  
Optimal Dose ◽  
Smooth Muscle Contraction ◽  
Beneficial Effects ◽  
Underlying Mechanisms

Cardiovascular diseases have overtaken cancers as the number one cause of death. Hypertension is the most dangerous factor linked to deaths caused by cardiovascular diseases. Many researchers have reported that tea has anti-hypertensive effects in animals and humans. The aim of this review is to update the information on the anti-hypertensive effects of tea in human interventions and animal studies, and to summarize the underlying mechanisms, based on ex-vivo tissue and cell culture data. During recent years, an increasing number of human population studies have confirmed the beneficial effects of tea on hypertension. However, the optimal dose has not yet been established owing to differences in the extent of hypertension, and complicated social and genetic backgrounds of populations. Therefore, further large-scale investigations with longer terms of observation and tighter controls are needed to define optimal doses in subjects with varying degrees of hypertensive risk factors, and to determine differences in beneficial effects amongst diverse populations. Moreover, data from laboratory studies have shown that tea and its secondary metabolites have important roles in relaxing smooth muscle contraction, enhancing endothelial nitric oxide synthase activity, reducing vascular inflammation, inhibiting rennin activity, and anti-vascular oxidative stress. However, the exact molecular mechanisms of these activities remain to be elucidated.

scholarly journals Calorie Restriction: Is AMPK a Key Sensor and Effector?

Physiology ◽  
2011 ◽  
Vol 26 (4) ◽  
pp. 214-224 ◽  
Author(s):  
Carles Cantó ◽  
Johan Auwerx
Keyword(s):  
Protein Kinase ◽  
Life Span ◽  
Calorie Restriction ◽  
Energy Availability ◽  
Beneficial Effects ◽  
Extend Life Span ◽  
Energy Sensor ◽  
External Cues ◽  
Amp Activated Protein Kinase

Dietary restriction can extend life span in most organisms tested to date, suggesting that mechanisms sensing nutrient and energy availability might regulate longevity. The AMP-activated protein kinase (AMPK) has emerged as a key energy sensor with the ability to transcriptionally reprogram the cell and metabolically adapt to external cues. In this review, we will discuss the possible role of AMPK in the beneficial effects of calorie restriction on health and life span.

Role of enzyme-peptide substrate backbone hydrogen bonding in determining protein kinase substrate specificities

Biochemistry ◽  
1987 ◽  
Vol 26 (14) ◽  
pp. 4461-4466 ◽  
Author(s):  
Nancy E. Thomas ◽  
H. Neal Bramson ◽  
W. Todd Miller ◽  
E. T. Kaiser
Keyword(s):  
Hydrogen Bonding ◽  
Protein Kinase ◽  
Peptide Substrate ◽  
Substrate Specificities ◽  
Kinase Substrate

scholarly journals Mouse models of altered protein kinase A signaling

2009 ◽  
Vol 16 (3) ◽  
pp. 773-793 ◽  
Author(s):  
Lawrence S Kirschner ◽  
Zhirong Yin ◽  
Georgette N Jones ◽  
Emilia Mahoney
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Mouse Models ◽  
Physiological Role ◽  
Gene Families ◽  
Current Data ◽  
Model Organisms ◽  
Signaling System ◽  
Kinase A

Protein kinase A (PKA) is an evolutionarily conserved protein which has been studied in model organisms from yeast to man. Although the cAMP–PKA signaling system was the first mammalian second messenger system to be characterized, many aspects of this pathway are still not well understood. Owing to findings over the past decade implicating PKA signaling in endocrine (and other) tumorigenesis, there has been renewed interest in understanding the role of this pathway in physiology, particularly as it pertains to the endocrine system. Because of the availability of genetic tools, mouse modeling has become the pre-eminent system for studying the physiological role of specific genes and gene families as a means to understanding their relationship to human diseases. In this review, we will summarize the current data regarding mouse models that have targeted the PKA signaling system. These data have led to a better understanding of both the complexity and the subtlety of PKA signaling, and point the way for future studies, which may help to modulate this pathway for therapeutic effect.

scholarly journals Erratum

1992 ◽  
Vol 12 (4) ◽  
pp. 707-707 ◽  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Protein Kinase C ◽  
Cerebral Blood Flow ◽  
Protein Kinase ◽  
Vertical Axis ◽  
Smooth Muscle Contraction ◽  
Kinase C ◽  
Chronic Cerebral Vasospasm

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm Tohru Matsui, Yoh Takuwa, Hiroo Johshita, Kamejiro Yamashita, and Takao Asano [Originally published in Journal of Cerebral Blood Flow and Metabolism 1992;11:143–149] On page 147 of the above, the unit on the left vertical axis of Figure 3 was incorrectly shown as “DAG Level (fLmollmg . protein).” The correct unit is “nmollmg protein.” The figure is shown below. The authors regret this error. [Figure: see text]

Sign in / Sign up

Export Citation Format

Share Document