Overexpression of heat shock protein Hsp27 protects against cerulein-induced pancreatitis

Kubisch, Constanze H.; DiMagno, Matthew; Tietz, Anne B.; Welsh, Michael J.; Ernst, Stephen A.; Brandt-Nedelev, Barbara; Diebold, Joachim; Wagner, Andreas; Göke, Burkhard; Williams, John A.; Schäfer, Claus

doi:10.1053/j.gastro.2004.04.005

Cited by 73 publications

(91 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A number of reports using HSF1-null mice and/or transgenic mice expressing HSP70 have shown that HSF1-dependent induction of HSP expression is protective against the development of various diseases, such as gastric ulcers, heart failure, pancreatitis, hypoxic/ischemic brain injury, and spinal and bulbar muscular atrophy (42)(43)(44)(45)(46). Because some HSPs have been reported to be overexpressed in the intestinal tissues of IBD patients (19,20,23) and in an animal model of IBD (21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Tanaka

Namba

Arai

et al. 2007

Journal of Biological Chemistry

130

124

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) involves infiltration of leukocytes into intestinal tissue, resulting in intestinal damage induced by reactive oxygen species (ROS). Pro-inflammatory cytokines and cell adhesion molecules (CAMs) play important roles in this infiltration of leukocytes. The roles of heat shock factor 1 (HSF1) and heat shock proteins (HSPs) in the development of IBD are unclear. In this study, we examined the roles of HSF1 and HSPs in an animal model of IBD, dextran sulfate sodium (DSS)-induced colitis. The colitis worsened or was ameliorated in HSF1-null mice or transgenic mice expressing HSP70 (or HSF1), respectively. Administration of DSS up-regulated the expression of HSP70 in colonic tissues in an HSF1-dependent manner. Expression of pro-inflammatory cytokines and CAMs and the level of cell death observed in colonic tissues were increased or decreased in DSS-treated HSF1-null mice or transgenic mice expressing HSP70, respectively, relative to control wild-type mice. Relative to macrophages from control wildtype mice, macrophages prepared from HSF1-null mice or transgenic mice expressing HSP70 displayed enhanced or reduced activity, respectively, for the generation of pro-inflammatory cytokines in response to lipopolysaccharide stimulation. Suppression of HSF1 or HSP70 expression in vitro stimulated lipopolysaccharide-induced up-regulation of CAMs or ROS-induced cell death, respectively. This study provides the first genetic evidence that HSF1 and HSP70 play a role in protecting against DSS-induced colitis. Furthermore, this protective role seems to involve various mechanisms, such as suppression of expression of pro-inflammatory cytokines and CAMs and ROS-induced cell death. Inflammatory bowel disease (IBD),2 Crohn disease, and ulcerative colitis have become substantial health problems with an actual prevalence of 200 -500 cases/100,000 people in western countries, which almost double every 10 years (1). Although the etiology of IBD is not yet fully understood, recent studies suggest that IBD involves chronic inflammatory disorders in the intestine because of "a vicious cycle." Infiltration into intestinal tissues causes intestinal mucosal damage induced by reactive oxygen species (ROS) that are released from the activated leukocytes, and this intestinal mucosal damage further stimulates the infiltration of leukocytes (2). To understand the molecular mechanism underlying the pathogenesis of IBD and to develop new types of clinical drugs for IBD, identification of endogenous factors that positively or negatively affect the development of IBD is important. For this purpose, various experimental animal colitis models, in particular the dextran sulfate sodium (DSS)-and trinitrobenzenesulfonic acid-induced colitis models, have been used (3).Pro-inflammatory cytokines play an important role in the activation and infiltration of leukocytes that are associated with IBD. This conclusion is supported by a range of evidence. Increases in the levels of various pro-inflammatory cytokines (such as tumor necr...

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Tanaka

Namba

Arai

et al. 2007

Journal of Biological Chemistry

130

124

View full text Add to dashboard Cite

show abstract

“…For mutant HSP27 vectors, the cDNA of HSP27 had been mutated at serine residues 15, 78, and 82 to aspartate (3D) to imitate the phosphorylated HSP27 form or mutated at the same residues to alanine (3A) to prevent phosphorylation of HSP27 (17). A constitutively active MEK1 cDNA was the generous gift from Dr. N. G. Ahn (Howard Hughes Medical Institute, University of Colorado, Boulder) (18).…”

Section: Methodsmentioning

confidence: 99%

Phosphorylated Heat Shock Protein 27 Represses Growth of Hepatocellular Carcinoma via Inhibition of Extracellular Signal-regulated Kinase

Matsushima‐Nishiwaki

Takai

Adachi

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Heat shock protein 27, one of the low molecular weight stress proteins, is recognized as a molecular chaperone; however, other functions have not yet been well established. Phosphorylated heat shock protein 27 levels inversely correlate with the progression of human hepatocellular carcinoma. This study shows that phosphorylated heat shock protein 27 interferes with cell growth of the hepatocellular carcinoma-derived HuH7 cells in the presence of the proinflammatory cytokine, tumor necrosis factor-␣, via inhibition of the sustained activation of the extracellular signal-regulated kinase signal pathway. The activities of Raf/extracellular signal-regulated kinase and subsequent activator protein-1 transactivation and the induction levels of cyclin D1 were lower in HuH7 cells transfected with phosphorylated heat shock protein 27 than those with unphosphorylated heat shock protein 27. Moreover, phosphorylated heat shock protein 27 up-regulated the levels of p38 mitogen-activated protein kinase and mitogen-activated protein kinase phosphatase-1, an inhibitory protein of extracellular signal-regulated kinase. These results indicate that phosphorylated heat shock protein 27 might suppress the extracellular signal-regulated kinase activity in the hepatocellular carcinoma cells via two separate pathways in an inflammatory state. The extracellular signal-regulated kinase activity is inversely correlated with phosphorylated heat shock protein 27 at serine 15 and also in human hepatocellular carcinoma tissues in vivo. Because the extracellular signal-regulated kinase signal pathway is a major proliferation signal of hepatocellular carcinoma, activator protein-1 activation is an early event in hepatocarcinogenesis. These findings strongly suggest that the control of the phosphorylated heat shock protein 27 levels could be a new therapeutic strategy especially to counter the recurrence of hepatocellular carcinoma.The mammalian small stress protein, heat shock protein (HSP) 2 27, is a widely expressed 27-kDa protein, and it is one of 10 members of the human low molecular weight HSP family. HSPs are classified into high molecular weight HSPs such as HSP70 and HSP90, and low molecular weight HSPs with molecular masses from 10 to 30 kDa based on their apparent molecular sizes. Low molecular weight HSPs have significant similarities in terms of amino acid sequences, known as the ␣-crystallin domain and WDPF motif (1, 2). The high molecular weight HSPs act as molecular chaperones in protein folding, oligomerization, and translocation (1). Although the functions of low molecular weight HSPs are not as well characterized as those of the high molecular weight HSPs, it is recognized that they may have chaperone activities (1). The functions of HSP27 are regulated by post-translational modifications such as phosphorylation (3, 4). Mouse HSP27 is phosphorylated at two sites (Ser-15 and Ser-82), whereas human HSP27 is phosphorylated at three sites (Ser-15, Ser-78, and Ser-82) (3). Ser-78 and Ser-82 of HSP27 are adjacent to the amino-termin...

show abstract

“…After CCK-8 stimulation acini were spun down and the supernatant was used to quantify amylase release as previously described (21). Net stimulated secretion of amylase in percent (%) was calculated by subtracting the secretion in the absence of secretagogue ("basal" secretion) from the secretion of amylase noted in the presence of CCK-8 ("stimulated" secretion).…”

Section: Quantification Of Pancreatic Acini Amylase Secretionmentioning

confidence: 99%

“…The homogenate was used to determine the trypsin activity as described (21). The concentration was calculated by using standards generated by purified trypsin.…”

Section: Trypsin Activity In Pancreatic Acinimentioning

confidence: 99%

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini

Malo¹,

Krüger

Seyhun

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

Overexpression of heat shock protein Hsp27 protects against cerulein-induced pancreatitis

Cited by 73 publications

References 36 publications

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Phosphorylated Heat Shock Protein 27 Represses Growth of Hepatocellular Carcinoma via Inhibition of Extracellular Signal-regulated Kinase

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini

Contact Info

Product

Resources

About