Sepsis: Prognostic role of apoptosis regulators in gastrointestinal cells

Evangelos Messaris, Panagiotis Kekis, Nicolaos Memos, Emmy Chatzigianni, Evangelos Menenakos, Emanuel Leandros, Manousos M. Konstadoulakis

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Intestinal epithelial cell apoptosis has been reported in sepsis as a mechanism of organ failure. The aim of this study was to clarify the role of apoptosis-regulating proteins (bcl-2, bax, cytochrome-c, and caspase-8) in septic rats by studying their expression in gastric and intestinal epithelial cells. Methods: Adult Wistar rats were subjected to the cecal ligation and puncture (CLP) model of sepsis and randomly divided into two study groups. Sixty-two animals were sacrificed 6, 12, 24, 36, 48, and 60 h post-procedure, and 50 animals served as the survival study group. Sham-operated animals (n = 40) were used as controls. Gastric and intestinal tissue was excised, and immunohistochemical detection of bcl-2, bax, cytochrome-c, and caspase-8 protein expression was performed. Results: In gastric mucosa, sepsis induced upregulation of bax and downregulation of caspase-8 expression (p = 0.053 and p = 0.05, respectively). Both bax and caspase-8 were upregulated as early as 6 h post CLP and progressively decreased (p = 0.001, p = 0.004 respectively). In contrast, the expression of the anti-apoptotic bcl-2 was upregulated progressively during the sepsis syndrome (p = 0.03). In intestine, sepsis induced a fourfold upregulation of the cytoprotective bcl-2 (p = 0.0001), accompanied by a remarkable increase in bax (p = 0.002) and caspase-8 (p = 0.0001) expression and a decrease in cytochrome-c expression (p = 0.02). The time distribution of the apoptosis regulators followed the same pattern as in gastric tissue, showing an upregulation of the proapoptotic bax and cytochrome c (p = 0.04) during the early phases and a progressively increased expression of bcl-2 during the late phases (p = 0.0001). Bax expression in gastric epithelium of subjects with septic syndrome was detrimental to survival (p = 0.0001), whereas the expression of the cytoprotective bcl-2 in intestinal epithelium appeared to favor a good prognosis (p = 0.0001). Conclusions: Sepsis results in alterations of apoptosis regulators in gastrointestinal cells. Alterations of bax and bcl-2 expression in gastric and intestinal epithelial cells may predict the outcome in septic rats.

Original languageEnglish (US)
Pages (from-to)787-794
Number of pages8
JournalWorld Journal of Surgery
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2007

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Caspase 8
Sepsis
Stomach
Cytochromes c
Apoptosis
Up-Regulation
Epithelial Cells
Punctures
Ligation
Systemic Inflammatory Response Syndrome
Intestinal Mucosa
Gastric Mucosa
Intestines
Wistar Rats
Proteins
Down-Regulation
Epithelium

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Messaris, E., Kekis, P., Memos, N., Chatzigianni, E., Menenakos, E., Leandros, E., & Konstadoulakis, M. M. (2007). Sepsis: Prognostic role of apoptosis regulators in gastrointestinal cells. World Journal of Surgery, 31(4), 787-794. https://doi.org/10.1007/s00268-005-0742-1
Messaris, Evangelos ; Kekis, Panagiotis ; Memos, Nicolaos ; Chatzigianni, Emmy ; Menenakos, Evangelos ; Leandros, Emanuel ; Konstadoulakis, Manousos M. / Sepsis : Prognostic role of apoptosis regulators in gastrointestinal cells. In: World Journal of Surgery. 2007 ; Vol. 31, No. 4. pp. 787-794.
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abstract = "Background: Intestinal epithelial cell apoptosis has been reported in sepsis as a mechanism of organ failure. The aim of this study was to clarify the role of apoptosis-regulating proteins (bcl-2, bax, cytochrome-c, and caspase-8) in septic rats by studying their expression in gastric and intestinal epithelial cells. Methods: Adult Wistar rats were subjected to the cecal ligation and puncture (CLP) model of sepsis and randomly divided into two study groups. Sixty-two animals were sacrificed 6, 12, 24, 36, 48, and 60 h post-procedure, and 50 animals served as the survival study group. Sham-operated animals (n = 40) were used as controls. Gastric and intestinal tissue was excised, and immunohistochemical detection of bcl-2, bax, cytochrome-c, and caspase-8 protein expression was performed. Results: In gastric mucosa, sepsis induced upregulation of bax and downregulation of caspase-8 expression (p = 0.053 and p = 0.05, respectively). Both bax and caspase-8 were upregulated as early as 6 h post CLP and progressively decreased (p = 0.001, p = 0.004 respectively). In contrast, the expression of the anti-apoptotic bcl-2 was upregulated progressively during the sepsis syndrome (p = 0.03). In intestine, sepsis induced a fourfold upregulation of the cytoprotective bcl-2 (p = 0.0001), accompanied by a remarkable increase in bax (p = 0.002) and caspase-8 (p = 0.0001) expression and a decrease in cytochrome-c expression (p = 0.02). The time distribution of the apoptosis regulators followed the same pattern as in gastric tissue, showing an upregulation of the proapoptotic bax and cytochrome c (p = 0.04) during the early phases and a progressively increased expression of bcl-2 during the late phases (p = 0.0001). Bax expression in gastric epithelium of subjects with septic syndrome was detrimental to survival (p = 0.0001), whereas the expression of the cytoprotective bcl-2 in intestinal epithelium appeared to favor a good prognosis (p = 0.0001). Conclusions: Sepsis results in alterations of apoptosis regulators in gastrointestinal cells. Alterations of bax and bcl-2 expression in gastric and intestinal epithelial cells may predict the outcome in septic rats.",
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Messaris, E, Kekis, P, Memos, N, Chatzigianni, E, Menenakos, E, Leandros, E & Konstadoulakis, MM 2007, 'Sepsis: Prognostic role of apoptosis regulators in gastrointestinal cells', World Journal of Surgery, vol. 31, no. 4, pp. 787-794. https://doi.org/10.1007/s00268-005-0742-1

Sepsis : Prognostic role of apoptosis regulators in gastrointestinal cells. / Messaris, Evangelos; Kekis, Panagiotis; Memos, Nicolaos; Chatzigianni, Emmy; Menenakos, Evangelos; Leandros, Emanuel; Konstadoulakis, Manousos M.

In: World Journal of Surgery, Vol. 31, No. 4, 01.04.2007, p. 787-794.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sepsis

T2 - Prognostic role of apoptosis regulators in gastrointestinal cells

AU - Messaris, Evangelos

AU - Kekis, Panagiotis

AU - Memos, Nicolaos

AU - Chatzigianni, Emmy

AU - Menenakos, Evangelos

AU - Leandros, Emanuel

AU - Konstadoulakis, Manousos M.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - Background: Intestinal epithelial cell apoptosis has been reported in sepsis as a mechanism of organ failure. The aim of this study was to clarify the role of apoptosis-regulating proteins (bcl-2, bax, cytochrome-c, and caspase-8) in septic rats by studying their expression in gastric and intestinal epithelial cells. Methods: Adult Wistar rats were subjected to the cecal ligation and puncture (CLP) model of sepsis and randomly divided into two study groups. Sixty-two animals were sacrificed 6, 12, 24, 36, 48, and 60 h post-procedure, and 50 animals served as the survival study group. Sham-operated animals (n = 40) were used as controls. Gastric and intestinal tissue was excised, and immunohistochemical detection of bcl-2, bax, cytochrome-c, and caspase-8 protein expression was performed. Results: In gastric mucosa, sepsis induced upregulation of bax and downregulation of caspase-8 expression (p = 0.053 and p = 0.05, respectively). Both bax and caspase-8 were upregulated as early as 6 h post CLP and progressively decreased (p = 0.001, p = 0.004 respectively). In contrast, the expression of the anti-apoptotic bcl-2 was upregulated progressively during the sepsis syndrome (p = 0.03). In intestine, sepsis induced a fourfold upregulation of the cytoprotective bcl-2 (p = 0.0001), accompanied by a remarkable increase in bax (p = 0.002) and caspase-8 (p = 0.0001) expression and a decrease in cytochrome-c expression (p = 0.02). The time distribution of the apoptosis regulators followed the same pattern as in gastric tissue, showing an upregulation of the proapoptotic bax and cytochrome c (p = 0.04) during the early phases and a progressively increased expression of bcl-2 during the late phases (p = 0.0001). Bax expression in gastric epithelium of subjects with septic syndrome was detrimental to survival (p = 0.0001), whereas the expression of the cytoprotective bcl-2 in intestinal epithelium appeared to favor a good prognosis (p = 0.0001). Conclusions: Sepsis results in alterations of apoptosis regulators in gastrointestinal cells. Alterations of bax and bcl-2 expression in gastric and intestinal epithelial cells may predict the outcome in septic rats.

AB - Background: Intestinal epithelial cell apoptosis has been reported in sepsis as a mechanism of organ failure. The aim of this study was to clarify the role of apoptosis-regulating proteins (bcl-2, bax, cytochrome-c, and caspase-8) in septic rats by studying their expression in gastric and intestinal epithelial cells. Methods: Adult Wistar rats were subjected to the cecal ligation and puncture (CLP) model of sepsis and randomly divided into two study groups. Sixty-two animals were sacrificed 6, 12, 24, 36, 48, and 60 h post-procedure, and 50 animals served as the survival study group. Sham-operated animals (n = 40) were used as controls. Gastric and intestinal tissue was excised, and immunohistochemical detection of bcl-2, bax, cytochrome-c, and caspase-8 protein expression was performed. Results: In gastric mucosa, sepsis induced upregulation of bax and downregulation of caspase-8 expression (p = 0.053 and p = 0.05, respectively). Both bax and caspase-8 were upregulated as early as 6 h post CLP and progressively decreased (p = 0.001, p = 0.004 respectively). In contrast, the expression of the anti-apoptotic bcl-2 was upregulated progressively during the sepsis syndrome (p = 0.03). In intestine, sepsis induced a fourfold upregulation of the cytoprotective bcl-2 (p = 0.0001), accompanied by a remarkable increase in bax (p = 0.002) and caspase-8 (p = 0.0001) expression and a decrease in cytochrome-c expression (p = 0.02). The time distribution of the apoptosis regulators followed the same pattern as in gastric tissue, showing an upregulation of the proapoptotic bax and cytochrome c (p = 0.04) during the early phases and a progressively increased expression of bcl-2 during the late phases (p = 0.0001). Bax expression in gastric epithelium of subjects with septic syndrome was detrimental to survival (p = 0.0001), whereas the expression of the cytoprotective bcl-2 in intestinal epithelium appeared to favor a good prognosis (p = 0.0001). Conclusions: Sepsis results in alterations of apoptosis regulators in gastrointestinal cells. Alterations of bax and bcl-2 expression in gastric and intestinal epithelial cells may predict the outcome in septic rats.

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Messaris E, Kekis P, Memos N, Chatzigianni E, Menenakos E, Leandros E et al. Sepsis: Prognostic role of apoptosis regulators in gastrointestinal cells. World Journal of Surgery. 2007 Apr 1;31(4):787-794. https://doi.org/10.1007/s00268-005-0742-1