Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P11021 (
BiP
)
2,049
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cystathionine gamma-lyase
(
CSE
) is a key enzyme in the trans-sulfuration pathway, which uses L-cysteine to produce hydrogen sulfide (H2S). Functional changes of pancreatic beta cells induced by endogenous H2S have been reported, but the effect of the
CSE
/H2S system on pancreatic beta cell survival has not been known. In this study, we demonstrate that H2Sat physiologically relevant concentrations induced apoptosis of INS-1E cells, an insulin-secreting beta cell line. Transfection of INS-1E cells with a recombinant defective adenovirus containing the
CSE
gene (Ad-CSE) resulted in a significant increase in
CSE
expression and H2S production. Ad-
CSE
transfection also stimulated apoptosis. The other two end products of
CSE
-catalyzed enzymatic reaction, ammonium and pyruvate, had no effects on INS-1E cell apoptosis, indicating that overexpression of
CSE
may stimulate INS-1E cell apoptosis via increased endogenous production of H2S. Both exogenous H2S (100 microM) and Ad-
CSE
transfection inhibited ERK1/2 but activated p38 MAPK. Interestingly,
BiP
and CHOP, two indicators of endoplasmic reticulum (ER) stress, were up-regulated in H2S-and
CSE
-mediated apoptosis in INS-1E cells. After suppressing CHOP mRNA expression, H2S-induced apoptosis of INS-1E cells was significantly decreased. Inhibition of p38 MAPK, but not of ERK1/2, inhibited the expression of
BiP
and CHOP and decreased H2S-stimulated apoptosis, suggesting that p38 MAPK activation functions upstream of ER stress to initiate H2S-induced apoptosis. It is concluded that H2S induces apoptosis of insulin-secreting beta cells by enhancing ER stress via p38 MAPK activation. Our findings may help unmask a novel role of
CSE
/H2S system in regulating pancreatic functions under physiological condition and in diabetes.
...
PMID:H2S, endoplasmic reticulum stress, and apoptosis of insulin-secreting beta cells. 1743 Aug 88
