Musch M W, Hayden D, Sugi K, Straus D, Chang E B
Inflammatory Bowel Disease Center, University of Chicago, IL 60637, USA.
Proc Assoc Am Physicians. 1998 Mar-Apr;110(2):136-9.
Glutamine is a major metabolic fuel and trophic agent for intestinal epithelial cells that can enhance intestinal epithelial cell survival against oxidant and thermal stress, possibly through the induction of heat shock protein 72 (hsp72). In this study, we examined the possibility of a direct causal relationship and tissue specificity of glutamine-induced hsp72. Glutamine treatment of intestinal (epithelial) IEC18 cells, but not HeLa (epidermoid) cells, induces the production of hsp72 in a concentration-dependent fashion, without affecting the expression of the constitutively expressed heat shock protein, hsc73. To determine the specific role that hsp72 induction by glutamine plays in resistance of IEC18 cells to oxidant injury, stable transfected cells expressing an hsp72 antisense construct were established. Although thermal induction of hsp72 was blocked only partially by the antisense construct, glutamine induction of hsp72 was completely inhibited. This was associated with a loss of the protective effects of glutamine against oxidant-induced stress. Thus, glutamine specifically induces hsp72 in intestinal epithelial cells, which mediates cell protection against inflammation-induced stress such as oxidants.
谷氨酰胺是肠上皮细胞的主要代谢燃料和营养因子，它可能通过诱导热休克蛋白72（hsp72）来提高肠上皮细胞在抗氧化和热应激下的存活率。在本研究中，我们研究了谷氨酰胺诱导hsp72产生的直接因果关系和组织特异性。用谷氨酰胺处理肠（上皮）IEC18细胞，而非HeLa（表皮样）细胞，可浓度依赖性地诱导hsp72的产生，且不影响组成型表达的热休克蛋白hsc73的表达。为了确定谷氨酰胺诱导hsp72在IEC18细胞抵抗氧化损伤中的具体作用，我们构建了稳定转染表达hsp72反义构建体的细胞。虽然反义构建体仅部分阻断了hsp72的热诱导，但谷氨酰胺诱导hsp72的作用被完全抑制。这与谷氨酰胺对氧化应激的保护作用丧失有关。因此，谷氨酰胺特异性地在肠上皮细胞中诱导hsp72，后者介导细胞对炎症诱导的应激（如氧化剂）的保护作用。
