Pancreatic stellate cells serve as a brake mechanism on pancreatic acinar cell calcium signaling modulated by methionine sulfoxide reductase expression
Pancreatic stellate cells serve as a brake mechanism on pancreatic acinar cell calcium signaling modulated by methionine sulfoxide reductase expression
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作者：
Liu JS;Cui ZJ
Background / Objectives: Although methionine sulfoxide reductase (Msr) is known to modulate the activity of a variety of functional proteins, the possible roles of Msr in pancreatic stellate cell physiology have not been reported. Therefore in the present work we have investigated the expression and function of Msr in the freshly isolated and cultured rat pancreatic stellate cells. Methods: Rat pancreatic stellate cells were isolated and cultured. Msr expression was determined by RT-PCR, Western blot and immunocytochemistry. Msr over-expression was achieved with adenovirus vector transfection. Pancreatic stellate cells were co-cultured with pancreatic acinar cells AR4-2J in monolayer culture to assess stellate cell modulation of acinar cell function. Pancreatic stellate and acinar cell function was gauged by Fura-2 fluorescent calcium imaging. Results: Rat pancreatic stellate cells were found to express MsrA, B1, B2, their expressions diminished in culture. Over-expressions of MsrA, B1, or B2 were found to enhance ATP-stimulated calcium increase but decreased reactive oxygen species production and lipopolysaccharide-elicited IL-1 production. Pancreatic stellate cell-co-culture with AR4-2J blunted cholecystokinin- and acetylcholine-stimulated calcium increases in AR4-2J, depending on acinar / stellate cell ratio. Pancreatic stellate cell MsrA, B1 over-expression or Met supplementation in the co-culture medium restored cholecystokinin-induced calcium oscillations in AR4-2J. Conclusion: The above data suggest that pancreatic stellate cells serve as a brake mechanism on pancreatic acinar cells which is modulated by Msr expression.
