Differential Protection of Primary Rat Cardiocytes by Transfection of Specific Heat Stress Proteins

Cumming, D. V. E.; Heads, Richard J.; Watson, Andrea; Latchman, David S.; Yellon, Derek M.

doi:10.1006/jmcc.1996.0227

Cited by 64 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40 Enhanced HSP70 protein levels protect against lethal heat stress and ischemia. 41 ROS such as H 2 O 2 have pleiomorphic effects on cells, eliciting apoptosis in some cell types 42 while stimulating early growth-response gene expression and proliferation in others. 5 The cell types that exhibit proliferative responses likely have adaptive mechanisms to overcome the adverse effects of oxidants.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway

Madamanchi

Patterson

et al. 2001

ATVB

210

149

View full text Add to dashboard Cite

Abstract-Reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ) activate intracellular signal transduction pathways implicated in the pathogenesis of cardiovascular disease. H 2 O 2 is a mitogen for rat vascular smooth muscle cells (VSMCs), and protein tyrosine phosphorylation is a critical event in VSMC mitogenesis. Therefore, we investigated whether the mitogenic effects of H 2 O 2 , such as stimulation of extracellular signal-regulated kinase (ERK)2, are mediated via activation of cytoplasmic Janus tyrosine kinases (JAKs). JAK2 was activated rapidly in VSMCs treated with H 2 O 2 , and signal transducers and activators of transcription (STAT) STAT1 and STAT3 were tyrosine-phosphorylated and translocated to the nucleus in a JAK2-dependent manner. A ccumulating evidence supports a critical role for oxidative stress in the pathogenesis of atherosclerosis, cancer, and other human diseases. 1 High levels of reactive oxygen species (ROS) damage DNA and inactivate proteins, 2 resulting in chronic cellular dysfunction. Many cell types have also harnessed ROS, albeit in lower concentrations, as intracellular signaling molecules to mediate growth factor and cytokine responses. 3,4 Modulation of growth responses by ROS has been demonstrated in a number of cell types, including vascular smooth muscle cells (VSMCs). 5,6 Stimulation of VSMC proliferation by ROS is thought to be a critical step in atherosclerotic lesion formation. 7 Tyrosine phosphorylation of cellular proteins and the consequent induction of transcription of early-response genes are key determinants of cell growth and differentiation in response to mitogenic signaling. 8 VSMC mitogens such as platelet-derived growth factor and epidermal growth factor activate receptor protein tyrosine kinases on binding, which stimulate intracellular signaling pathways that result in mitogen-activated protein kinase activation. 9,10 Other mitogens, such as thrombin and angiotensin II, activate G proteincoupled receptors that do not possess intrinsic tyrosine kinase activity but require tyrosine phosphorylation events to induce mitogenesis. [11][12][13] The necessary role for protein tyrosine phosphorylation in mitogenesis elicited by thrombin and ROS indicates that these mitogens may utilize cytoplasmic protein tyrosine kinases in their signaling cascade. Forming 1 such group of tyrosine kinases are Janus kinases (JAKs), which along with their substrates, signal transducers and activators of transcription (STATs), have hitherto been characterized as essential mediators of cytokine and polypeptide hormone-induced signaling. 8,14 Members of the JAK/STAT pathway mediate at least some biological effects of angiotensin II, 15 plateletderived growth factor-BB, 15,16 and endothelial growth factor. 17 Activation of the JAK/STAT pathway has also been observed in response to generation of intracellular ROS 18 and exogenous hydrogen peroxide (H 2 O 2 ). 19 On phosphorylation by JAKs of tyrosine residues, activated STAT dimers translocate to the nucleus to transactivate tar...

show abstract

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway

Madamanchi

Patterson

et al. 2001

ATVB

210

149

View full text Add to dashboard Cite

show abstract

“…Hsp90 is normally abundant in the cytoplasm of normal cardiac cells and levels of the protein increase considerably in response to stress (Heads et al 1995). We have shown previously in our laboratory that over-expression of the hsp90 gene alone by transfection in the H9c2 cardiac cell line (Heads et al 1995) and primary cardiac myocytes (Cumming et al 1996) protects the cells from lethal heat shock, but not from hypoxic/ischaemic injury. This is in contrast to hsp70 which protects the cardiac cells from both stresses.…”

Section: Discussionmentioning

confidence: 98%

“…Hsp90 forms a complex with hsp70 and hsp56 and the steroid receptors (Denis & Gustafsson 1989). Overexpression of hsp90 has been shown to protect cardiac cells from lethal heat stress only and not from hypoxic injury (Heads et al 1995), although hsp90 protein expression has been shown to increase in ischaemic myocardium (Heads et al 1995, Cumming et al 1996.…”

Section: Introductionmentioning

confidence: 99%

Urocortin increases the expression of heat shock protein 90 in rat cardiac myocytes in a MEK1/2-dependent manner

Brar¹,

Railson²,

Stephanou³

et al. 2002

Journal of Endocrinology

View full text Add to dashboard Cite

We have previously demonstrated that urocortin protects cultured cardiac myocytes from ischaemic and reoxygenation injury and decreases the infarct size in the rat heart exposed to regional ischaemia and reperfusion. Urocortin-mediated cardioprotection is via activation of the mitogen-activated protein kinase (MAP kinase, MEK1/2) pathway. In addition, it is well documented that heat shock protein (hsp) 70 and hsp90 are cardioprotective against lethal stress. In this study we show, for the first time, that urocortin induces the expression of hsp90 but not hsp70 in primary cultures of rat neonatal cardiac myocytes. Levels of hsp90 protein increase by 1·5-fold over untreated cells within 10 min of urocortin treatment and are sustained for 24 h with a maximal increase of 2·5-fold at 60 min (P<0·05 at all time points). The increase in hsp90 expression by urocortin was not inhibited by actinomycin D, and urocortin failed to increase hsp90 promoter activity. Urocortin induction of hsp90 was inhibited by the MEK1/2 inhibitor PD98059 (P<0·001) and by cycloheximide, and both inhibitors abrogate urocortin-mediated cardioprotection (P<0·05 for cycloheximide, P<0·001 for PD98059). Hence, MEK1/2 and protein synthesis are involved in the cardioprotective effect of urocortin against hypoxic-mediated cell death, possibly due to an increase in expression of hsp90 protein. This is the first report of heat shock protein induction by urocortin or any other member of the corticotrophin-releasing hormone family.

show abstract

“…A shortage of HSPs associated with lesions in the myocardium may cause electromechanical dissociation, which can result in acute heart failure and death, as observed under poor environmental and management conditions, such as stressful transport (Luh et al, 2007). Although Hsp90 was able to protect cultured primary cardiac cells (Cumming et al, 1996), little information is available to support a specific role for Hsp90α and its expression in response to heat stress in primary cultures of cardiac myocytes in vitro. Although it has been demonstrated that a lack of HSP in cardiac cells results in acute heart failure (Amrani et al, 1993), the mechanisms by which Hsp90α offers protection against this remain unclear.…”

Section: +mentioning

confidence: 99%

“…Although the stress damage of myocardial cells still existed in the sustaining hyperthermia situation, these results showed that Hsp90α started to increase after 120 min and reached significantly high levels after 360 min of heat stress, while CK started to decrease. The over-expression of Hsp90 can protect either cultured primary cardiac cells (Cumming et al, 1996) or H9c2 cells against heat stress (Heads et al, 1995). However, the cytoprotective activity of Hsp90α was delayed in its action against heat stress at the beginning of the heat treatment, which could be attributed to the consumption of Hsp90α exceeding its production.…”

Section: A B Cmentioning

confidence: 99%

Expression of heat shock protein 90 alpha (Hsp90α) in primary neonatal rat myocardial cells exposed to various periods of heat stress in vitro

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. The objective of this study was to investigate the mechanism of heat shock protein 90 alpha (Hsp90α) protection against heart damage resulting from heat stress by detecting Hsp90α mRNA, Hsp90α protein, protein localization, and cell damage in primary myocardial cells of neonatal rats in response to heat stress in vitro. The cells were heat-stressed at 42°C in an incubator with 95% air and 5% CO 2 for different periods. Levels of Hsp90α, protein localization, enzymes, and cytopathological lesions were detected using Western blot, immunocytochemistry enzymatic assays, and cytopathological techniques. Aspartate aminotransferase, lactate Heat shock, Hsp90α and primary myocardial cells dehydrogenase, and creatine kinase enzyme levels were elevated during heat stress, and acute cellular lesions that were characterized by vacuolar degeneration and necrosis were observed. Hsp90α levels decreased between 10 and 60 min of heat stress and increased after 360 and 480 min, while Hsp90α mRNA decreased after 360 min. These results indicate that heat stress might induce irreversible damage in certain myocardial cells. The elevated Hsp90α level at the end of heat stress and its positive signal in the cytoplasm of myocardial cells after heat stress could be associated with its protective role. Additionally, the consumption of Hsp90α exceeded its production in the first period of treatment.

show abstract

Differential Protection of Primary Rat Cardiocytes by Transfection of Specific Heat Stress Proteins

Cited by 64 publications

References 0 publications

Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway

Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway

Urocortin increases the expression of heat shock protein 90 in rat cardiac myocytes in a MEK1/2-dependent manner

Expression of heat shock protein 90 alpha (Hsp90α) in primary neonatal rat myocardial cells exposed to various periods of heat stress in vitro

Contact Info

Product

Resources

About