Disease relevance of Igfals

• The effect of sustained endotoxemia on expression of the acid-labile subunit (ALS) in relation to hepatic markers of altered GH and insulin sensitivity was examined [1].
• Combination therapy with glucocorticoids and three injections of ALS reversed hyperglycemia in a significant number of acutely diabetic animals [2].
• In both these models, all the tumors were classified as adenocarcinomas, and most of the Als observed were confined to single tumors with atypical histopathology [3].
• Aberrant functioning of the glutamate uptake system seems to be linked to some neurodegenerative disorders (eg amyotrophic lateral sclerosis, ALS) [4].
• Als were observed in both transitional-cell carcinomas and papillomas, although most were in the carcinomas [3].

High impact information on Igfals

• Stem cells step closer to the clinic: paralysis partially reversed in rats with ALS-like disease [5].
• Recent studies suggest that the inducible isoform of cyclooxygenase, COX-2, promotes motor neuron loss in rodent models of ALS [6].
• Combination immunosuppression therapy with long-acting glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes (ALS) reduced the severity of spontaneous diabetes among BioBreeding/Worcester rats and decreased the frequency of diabetes in susceptible littermates [2].
• The administration of a short course of ALS (1 ml I.P. days-1, 1, 3 and 5) to the remaining 6 animals greatly prolonged graft survival with all animals remaining normoglycaemic for at lest 4 weeks [7].
• Malnutrition suppresses ALS and IGF-I expression in a development-dependent manner [8].

Chemical compound and disease context of Igfals

• Walker 256, Neuroblastoma, and Sarcoma dual-tumor models were used to evaluate the effect of ALS aspiration on the uptake of 3F8 monoclonal antibody, and doxorubicin [9].

Biological context of Igfals

• Serum ALS rose from 3 micrograms/ml in 2-day-old rats to more than 40 micrograms/ml at 10 weeks, with no sex difference [10].
• We have shown that gene expression of ALS is regulated by a number of factors, particularly growth hormone [11].
• The acid-labile subunit (ALS) of the ternary insulin-like growth factor-binding protein complex has a central role in controlling the bioavailability of circulating insulin-like growth factors [11].
• Southern analysis suggests a single copy of the ALS gene in the rat genome [11].
• ALS buffers the metabolic effects of the insulin-like growth factors by sequestering them in a ternary complex with insulin-like growth factor-binding protein-3 [12].

Anatomical context of Igfals

• We investigated the effects of PGE2, a principal downstream prostaglandin product of COX-2 activity, on motor neuron survival in an organotypic culture model of ALS [6].
• Circulating acid-labile subunit (ALS) is mainly hepatocyte derived and is GH dependent [12].
• Similarly, unresponsive WF recipients of BN grafts accepted second Lewis grafts after IT injection of Lewis T cells combined with ALS, 30 or 100 days after primary BN grafts [13].
• Failure to demonstrate a synergistic effect between enhancing serum and ALS in recipients of pancreatic islet allografts [14].
• Northern analysis of ALS messenger RNA (mRNA) from adult rat brain, heart, lung, muscle, spleen, testis or ovary, kidney, and liver showed a liver-specific predominant 2-kilobase transcript [15].

Associations of Igfals with chemical compounds

• A short course of procarbazine hydrochloride (PCH; 50 mg/kg) and antilymphocyte serum (ALS; 5 ml/kg), administered to Lewis (LEW;RT1(1] rats in the first week following transplantation of Brown Norway (BN;RT1n) kidneys, substantially prolonged allograft survival and induced long-term survival in 62% of the grafts [16].
• Streptozotocin-diabetic rats, untreated or treated with human GH for 5 days, had significantly decreased serum ALS levels and liver ALS mRNA abundance [15].
• Dexamethasone, an inhibitor of ALS synthesis by hepatocytes, significantly reduced both serum ALS and hepatic ALS mRNA [15].
• In the present study, the regulatory effects of the cAMP analogs dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP (8-br-cAMP) on IGF-I, ALS, and IGFBP expression were evaluated in primary cultures of rat hepatocytes, KC as well as in cocultures of hepatocytes and KC [17].
• The proposed excitotoxic mechanism of ALS, therefore, is most likely mediated through non-NMDA glutamate receptors [18].

Other interactions of Igfals

• The GH-dependent, hepatocyte-derived acid-labile subunit (ALS) regulates IGF release from the serum by forming ternary complexes containing IGF binding protein (IGFBP)-3 or IGFBP-5 [8].
• Neither regulation of hepatic GH receptor nor ALS clearance rates could explain the age-dependent effect [8].

Analytical, diagnostic and therapeutic context of Igfals

• Purification involved ion-exchange chromatography, and affinity chromatography on an IGF-I-IGFBP-3 column, yielding almost 1 mg ALS from 100 ml serum [10].
• Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS [19].
• By contrast, treatment with i.t. donor splenocytes plus ALS 2 weeks prior to transplantation prolonged graft survival (100% long-term; mean 90.0 +/- 0.0 days, P < 0.04), and markedly inhibited graft arteriosclerosis (score 0.80 +/- 0.14, P < 0.05; 27 +/- 4% diseased, P < 0.05) [20].
• Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model [21].
• Recipient F344 rats were treated with donor (Lewis) splenocytes by intrathymic injection (i.t.) alone (10 x 10(6) cells/lobe); with donor splenocytes i.t. plus a one-time dose of ALS (1 mg) by intraperitoneal injection (i.p.); or with ALS i.p. (1 mg) alone 2 and 6 weeks prior to heterotopic Lewis heart transplantation [20].

References