Insulin-induced myocardial protection in isolated ischemic rat hearts requires p38 MAPK phosphorylation of Hsp27

Li, Gefeng; Ali, Imtiaz S.; Currie, R. William

doi:10.1152/ajpheart.00675.2007

Cited by 21 publications

(17 citation statements)

References 77 publications

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“…The positive association of serum Hsp27 with FPG suggests that hyperglycaemia may be related to an increased cellular expression of Hsp27 leading to the higher serum concentration. Insulin has been shown to increase the expression of heat shock proteins or Hsp27 phosphorylation (Franklin et al 2008;Li et al 2008); however we did not find a significant relationship between serum insulin and Hsp27 concentrations in this study, and therefore our data do not indicate that insulin is a major determinant of serum Hsp27 in these groups of patients, although it may be a determinant of tissue levels of Hsp27. Hsp27 is constitutively expressed in many normal adult human tissues and different cell types including endothelial cells of the vasculature (Ciocca et al 1993;Portig et al 1996).…”

Section: Discussioncontrasting

confidence: 86%

Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study

Burut

Borai

Livingstone

et al. 2010

Cell Stress and Chaperones

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Heat shock protein 27 (Hsp27) is over-expressed when cells are exposed to stressful conditions that include oxidative stress. Oxidative stress has been implicated in the pathogenesis of cardiovascular disease (CVD), diabetes and insulin resistance. We have investigated the concentrations of serum Hsp27 antigen and antibodies in subjects from different glycaemic categories, who either did or did not have established CVD. Serum Hsp27 antigen and antibody levels (immunoglobulins M and G (IgM and IgG)) were determined by enzyme-linked immunosorbent assays (ELISAs) in 68 individuals: 26 with normal glucose tolerance (NGT), 10 with (+) and 16 without (-) a history of CVD and 42 individuals with varying degrees of glucose intolerance (GI; 21 with and 21 without a history of CVD). Insulin sensitivity was determined in each subject using indices derived from the homeostasis model assessment of sensitivity and the insulin sensitivity index for glycaemia. Serum Hsp27 concentrations were significantly higher in GI (+CVD) subjects compared to GI (-CVD) subjects (p = 0.03), NGT (-CVD) subjects (p = 0.02) and NGT (+CVD) subjects (p = 0.04) and were positively correlated to fasting plasma glucose for all subjects (r = 0.28, p = 0.03). IgM antibody levels were significantly higher in GI (+CVD) subjects compared to NGT (-CVD) group (p = 0.02) and were inversely related to fasting insulin concentrations (r = -0.27, p = 0.04) and the 2-h insulin concentrations (r = -0.29, p = 0.03) for all subjects. Serum IgG antibody levels were higher in GI (+CVD) group compared to GI (-CVD) group (p = 0.06). In conclusion, Hsp27 and its antibody concentrations appear to relate to the presence of cardiovascular complications in patients with GI.

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Section: Discussioncontrasting

confidence: 86%

Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study

Burut

Borai

Livingstone

et al. 2010

Cell Stress and Chaperones

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“…The p38α isoform appears to promote apoptosis via ROS production, and calcium overload (Dhingra et al, 2007). On the other hand, p38β seems to inhibit apoptosis by activating heat shock protein 27 (Hsp27), which prevents proteolysis of myofilament proteins (Li et al, 2008). …”

Section: The Mapk Family In the Healthy Heartmentioning

confidence: 99%

Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives

Javadov

Jang

Agostini

2014

Pharmacology & Therapeutics

126

125

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Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling and cross-talk with other signaling networks. The extensively studied MAPKs ERK1/2, p38, JNK, and ERK5, demonstrate unique intracellular signaling mechanisms, responding to a myriad of mitogens and stressors and influencing the signaling of cardiac development, metabolism, performance, and pathogenesis. Definitive relationships between MAPK signaling and cardiac dysfunction remain elusive, despite 30 years of extensive clinical studies and basic research of various animal/cell models, severities of stress, and types of stimuli. Still, several studies have proven the importance of MAPK cross-talk with mitochondria, powerhouses of the cell that provide over 80% of ATP for normal cardiomyocyte function and play a crucial role in cell death. Although many questions remain unanswered, there exists enough evidence to consider the possibility of targeting MAPK-mitochondria interactions in the prevention and treatment of heart disease. The goal of this review is to integrate previous studies into a discussion of MAPKs and MAPK-mitochondria signaling in cardiac diseases, such as myocardial infarction (ischemia), hypertrophy and heart failure. A comprehensive understanding of relevant molecular mechanisms, as well as challenges for studies in this area, will facilitate the development of new pharmacological agents and genetic manipulations for therapy of cardiovascular diseases.

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“…Paradoxically, at the end of reperfusion, phosphorylated p38 levels were increased in response to glucosamine treatment. This could lead to the activation of prosurvival pathways through downstream effectors, such as ␣B-crystallin and HSP27, both of which have been shown to play a role in ischemic protection (58,96,129,150,174) and are also targets for O-GlcNAc modification (178,208,209). Preliminary studies have also shown that ischemia-reperfusion alters the level of O-GlcNAc modification of glycogen phosphorylase b, mitochondrial aconitase 2, and the cytoskeletal protein vinculin (124).…”

Section: Protein O-glcnacylation and Cardiovascular Protectionmentioning

confidence: 99%

ProteinO-GlcNAcylation: a new signaling paradigm for the cardiovascular system

Laczy¹,

Hill²,

Wang³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

141

135

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The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ␤-N-acetylglucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification. Protein O-GlcNAcylation is rapidly emerging as a key regulator of critical biological processes including nuclear transport, translation and transcription, signal transduction, cytoskeletal reorganization, proteasomal degradation, and apoptosis. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are both major hallmarks of diabetes mellitus and diabetes-related cardiovascular complications. Conversely, there is a growing body of data demonstrating that the acute activation of O-GlcNAc levels is an endogenous stress response designed to enhance cell survival. Reports on the effect of altered O-GlcNAc levels on the heart and cardiovascular system have been growing rapidly over the past few years and have implicated a role for O-GlcNAc in contributing to the adverse effects of diabetes on cardiovascular function as well as mediating the response to ischemic injury. Here, we summarize our present understanding of protein O-GlcNAcylation and its effect on the regulation of cardiovascular function. We examine the pathways regulating protein O-GlcNAcylation and discuss, in more detail, our understanding of the role of O-GlcNAc in both mediating the adverse effects of diabetes as well as its role in mediating cellular protective mechanisms in the cardiovascular system. In addition, we also explore the parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O-GlcNAcylation in regulating cell function. hexosamine biosynthesis; protein O-glycosylation; ␤-N-acetylglucosamine transferase; diabetes mellitus POSTTRANSLATIONAL MODIFICATION (PTM) of proteins is a common mechanism for the modulation of protein function, location, and turnover. Although protein phosphorylation is probably the most widely studied form of PTM, there are many other PTMs, including acylation, ubiquitylation, methylation, acetylation, thiolation, nitration, and glycosylation (107). The focus of this review is protein glycosylation, specifically, O-glycosylation of nuclear and cytoplasmic proteins. Classical protein glycosylation occurs in the endoplasmic reticulum and Golgi, leading to the formation of stable and complex elongated oligosaccharide structures via both N-linkage on asparagine and O-linkage on the hydroxy amino acids serine and threonine in addition to hydroxyproline, hydroxylysine, and tyrosine residues of proteins that become secreted or membrane component glycoproteins (189). In contrast, glycosylation of nuclear and cytoplasmic proteins is a rapid and dynamic modification of serine or threonine residues by the O-linked attachment of the monosaccharide ␤-N-acetylglucosamine (OGlcNAc) (97,195); this process is referred to as protein O-GlcNAcylation to contrast it wi...

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Insulin-induced myocardial protection in isolated ischemic rat hearts requires p38 MAPK phosphorylation of Hsp27

Abstract: Li G, Ali IS, Currie RW. Insulin-induced myocardial protection in isolated ischemic rat hearts requires p38 MAPK phosphorylation of

Cited by 21 publications

References 77 publications

Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study

Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study

Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives

ProteinO-GlcNAcylation: a new signaling paradigm for the cardiovascular system

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