Impaired cytoprotective function of muscle in human gallbladders with cholesterol stones.
Acute cholecystitis develops in gallbladders (GB) with excessive bile cholesterol (Ch). Increased membrane Ch content affects membrane function and may affect PGE(2) receptors involved in the cytoprotection against acute inflammation. This study was aimed at determining whether the cytoprotective response to PGE(2) is affected by lithogenic bile with Ch. Muscle cells from human GB with cholesterol stones (ChS) or pigment stones (PS) were obtained by enzymatic digestion. PGE(2) levels were measured by radioimmunoassay, and activities of superoxide dismutase (SOD) and catalase were assayed by spectrophotometry. The contraction in response to H(2)O(2) in muscle cells from PS was 14 +/- 0.3%, not different from normal controls, and decreased after the cells were incubated with Ch-rich liposomes (P < 0.05), which increase the Ch content in the plasma membranes. In muscle cells from GB with ChS, H(2)O(2)-induced contraction was only 9.2 +/- 1.3% and increased to 14 +/- 0.2% after Ch-free liposome treatment to remove Ch from the plasma membranes (P < 0.01). H(2)O(2) caused a similar increase in the levels of lipid peroxidation and PGE(2) content in muscle cells from GBs with ChS and PS. However, the activities of SOD and catalase were significantly lower in muscle cells from GBs with ChS compared with those with PS. The binding capacity of PGE(2) receptors was also significantly lower in muscle cells from GBs with ChS compared with those with PS. In conclusion, the cytoprotective response to reactive oxygen species is reduced in muscle cells from GBs with ChS despite a normal increase in the cellular levels of PGE(2). This impaired cytoprotective response may be due to a dysfunction of PGE(2) receptors with decreased binding capacity resulting from excessive Ch levels in the plasma membrane.
Division of Gastroenterology, APC 421, 593 Eddy St., Providence, RI 02903, USA.
Zuo-Liang
ZL
Xiao
Joseph
J
Amaral
Piero
P
Biancani
Jose
J
Behar
D002374:Catalase / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005704:Gallbladder / Q000473:pathology*; D042882:Gallstones / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000473:pathology*; D016877:Oxidants / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011869:Radioligand Assay; D013482:Superoxide Dismutase / Q000378:metabolism
D008081:Liposomes; D016877:Oxidants; D011506:Proteins; D002784:Cholesterol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D015232:Dinoprostone