Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis‐dependent mechanism

Oksala, Niku; Oksala, Anni; Paavonen, Timo; Alhava, Esko; Paimela, Hannu

doi:10.1034/j.1600-0463.2003.1110408.x

Cited by 6 publications

(13 citation statements)

References 42 publications

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“…The experiments were performed as described previously [9][10][11]. Briefly, guinea pig stomach was removed and after seromuscular dissection, two equal halves of the fundic mucosae were mounted in Ussing chambers and perfused (37°C).…”

Section: Perfusion Of Gastric Mucosamentioning

confidence: 99%

“…Superficial injury was induced after the 150-min recovery period by exposure of the mucosal surface to 1.25 mol/l NaCl for 5 min. The experiment was continued thereafter for 180 min, which is required for the rapid epithelial restitution to occur [9][10][11] after which the samples for caspase-3 and Hsp60 analysis were collected. The experimental protocol was approved by the institutional committee for experimental animal use and research of Kuopio University.…”

Section: Perfusion Of Gastric Mucosamentioning

confidence: 99%

“…activation of the AA pathways [8]. We have shown that heat shock preconditioning followed by normothermic recovery, inducing a modest 2-to 3-fold increase of Hsp70 levels, exerts a general inhibition on restitution and proliferation after superficial injury by a mechanism, that involves eicosanoid pathways and de novo protein synthesis [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Heat Shock Preconditioning and Eicosanoid Pathways Modulate Caspase 3-Like Activity in Superficially Injured Isolated Guinea Pig Gastric Mucosa

Oksala

Alhava²,

Paimela³

2004

Eur Surg Res

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Background: After superficial mucosal injury, the disturbed gastric epithelial continuity is restored by cellular migration. Caspase-3 is an enzyme responsible for the execution of stress-induced apoptosis. Interestingly, heat shock proteins (Hsp) including Hsp60 are capable of modulating caspase-3 activity. Interestingly, we have demonstrated that heat shock preconditioning upregulates Hsp synthesis and inhibits restitution and cell proliferation via mechanisms related to de novo protein synthesis and eicosanoid pathways, both of which are crucial in the regulation of apoptosis and gastric mucosal defense systems. Aims: To assess whether caspase-3 activity is affected by heat shock preconditioning and associated pharmacological modulations after standard superficial injury to allow development of cytoprotective strategies. Methods: Guinea pig gastric mucosae were mounted and perfused in paired Ussing chambers. After heat shock (HS) preconditioning (42°C) for 30 min, a superficial injury was induced (1.25 mol/l NaCl) followed by 3 h recovery. For mechanistic studies, the mucosa was exposed to 30 µmol/l arachidonic acid (AA) as a substrate for eicosanoid pathways, to 50 µmol/l quercetin (Q) to inhibit lipoxygenases, to 50 µmol/l indomethacin (In) to inhibit cyclo-oxygenases, or to 150 µmol/l cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment, the mucosa was prepared for analysis of caspase-3 activity. Hsp60 expression was analyzed to monitor the induction of heat shock response. Results: HS upregulated Hsp60 expression, indicating induction of the heat shock response without an effect on basal caspase-3 activity. Superficial injury itself did not affect caspase-3 activity nor Hsp60 synthesis. In all the experiments, exposure to CHX abolished caspase-3 activity and Hsp60 synthesis. AA+Q increased, Q decreased, while In+AA and In+AA+Q abolished caspase-3 activity independent of alterations in Hsp60 synthesis. Upon exposure to In+Q, HS decreased caspase-3 activity and upregulated Hsp60 synthesis. Conclusion: Caspase-3 activity in isolated guinea pig gastric mucosa is regulated by mechanisms dependent on de novo protein synthesis and eicosanoid pathways but is not strictly related to Hsp synthesis. Upon modulation of the eicosanoid pathways, HS may be utilized to simultaneously decrease caspase-3 activity and increase Hsp synthesis. Modulations of the eicosanoid pathways may be utilized to reduce caspase-3 activity also upon normothermic conditions suggesting a novel mechanism by which caspase-3 is regulated in the gastric mucosa.

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Section: Perfusion Of Gastric Mucosamentioning

confidence: 99%

Section: Perfusion Of Gastric Mucosamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heat Shock Preconditioning and Eicosanoid Pathways Modulate Caspase 3-Like Activity in Superficially Injured Isolated Guinea Pig Gastric Mucosa

Oksala

Alhava²,

Paimela³

2004

Eur Surg Res

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“…However, the chaperons are also expressed at rather high level under physiological conditions to insure newly synthesized cellular proteins maturation. The expression of certain chaperons, particularly Hsp73, Hsp60 and Hsp27, in actively proliferating cells is increased, first of all, due to uprise of protein synthesis and respectively their requirement for folding, refolding and irreversibly denatured polypeptides degradation [1,5].…”

Section: The Concentration Of Tbk-active Products and Antioxidant Enzmentioning

confidence: 99%

“…However, the large amount of proteins, required in order to provide the correct spatial conformation, demands the participation of special proteins so called molecular chaperones or heat shock proteins. The participation and molecular mechanisms of chaperones expression during the progression of such gastrointestinal tract diseases such as stress ulcer, chronic gastritis, stomach and duodenum polyps, cancer of various esophagus segments etc., require more profound research [3][4][5]. Moreover, one of the cardinal problems of chaperone functioning in cells of gastrointestinal tract mucosa is the study of their participation in regulation of molecular mechanisms of apoptosis and proliferation [5][6][7].…”

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confidence: 99%

Dynamics of heat shock proteins quantity in rats’ gastric mucosa lysates upon chronic atrophic gastritis development

et al. 2008

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Heat Shock Preconditioning Induces Protein Carbonylation and Alters Antioxidant Protection in Superficially Injured Guinea Pig Gastric Mucosa In Vitro

et al. 2007

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According to our previous studies, heat shock preconditioning of gastric mucosa requires modulation of protein synthesis and eicosanoid pathways to induce protection against superficial injury. This may be caused by heat shock-induced oxidative stress. We studied the effect of heat shock preconditioning with normothermic recovery on redox status in superficially injured (1.25 mmol NaCl for 5 min) Ussing chamber perfused guinea pig gastric mucosa allowed to recover for 3 hr after injury. Protein oxidation, lipid peroxidation, level of superoxide dismutase, level of heat shock protein 72 (HSP72), and level of oxygen radical absorbance capacity were measured. Superficial injury increased lipid peroxidation. Heat shock preconditioning decreased oxygen radical absorbance capacity and increased protein carbonyl and HSP72 levels, but inhibited electrophysiologic recovery. Exposure to indomethacin and arachidonic acid (AA) partially abolished this pro-oxidative and inhibitory effect on recovery, but maintained HSP72 levels and decreased protein carbonyls, lipid peroxidation, and oxygen radical absorbance capacity. In conclusion, superficial injury increased lipid peroxidation. Heat shock preconditioning alone induced oxidative stress via indomethacin- and AA-sensitive mechanisms. The development of optimal cytoprotective strategy may therefore require control of oxidative stress and modulation of the eicosanoid pathways.

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Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis‐dependent mechanism

Cited by 6 publications

References 42 publications

Heat Shock Preconditioning and Eicosanoid Pathways Modulate Caspase 3-Like Activity in Superficially Injured Isolated Guinea Pig Gastric Mucosa

Heat Shock Preconditioning and Eicosanoid Pathways Modulate Caspase 3-Like Activity in Superficially Injured Isolated Guinea Pig Gastric Mucosa

Dynamics of heat shock proteins quantity in rats’ gastric mucosa lysates upon chronic atrophic gastritis development

Heat Shock Preconditioning Induces Protein Carbonylation and Alters Antioxidant Protection in Superficially Injured Guinea Pig Gastric Mucosa In Vitro

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