PubMed · 10050791
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E Abboud, E Weisenberg, S Khan, D P Rhone. 1999. Pathologic quiz case.. https://doi.org/10.5858/1999-123-0157-pqc
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Mn(2+) treatment has been shown to promote neurite outgrowth in rat pheochromocytoma (PC12) cells in a time- and dose-dependent manner. This process is mediated through the interactions of extracellular matrix (ECM) proteins and integrin receptors. Studies were performed to determine whether the phosphorylation of the MAP kinases, ERK1 and 2, is required for Mn(2+)-induced neurite outgrowth. A time- and dose-dependent increase in phosphorylation of both ERK1 and 2 was observed upon treatment of PC12 cells with Mn(2+). Phosphorylation of the ERKs occurred as early as 2 hr after initiating treatment, with a maximum increase occurring at approximately 24 hr. Inhibition of MEK with the specific inhibitor, PD98059, blocked the phosphorylation of ERK1 and 2 and increased Mn(2+) toxicity. When cells were grown in serum-free defined medium, Mn(2+)-induced phosphorylation of ERK1 and ERK2 occurred in cells grown on surfaces treated with growth serum or fibronectin but not on surfaces treated with poly-L-lysine. In addition, the pentapeptide GRGDS, which blocks RGD-mediated interactions, inhibited Mn(2+)-induced phosphorylation of ERK1 and 2. The Mn(2+)-induced increase in phosphorylated ERK1 and 2 was not seen in a PC12 cell line that does not respond to Mn(2+). These data support the hypothesis that integrin-mediated activation of the MAPK signal transduction pathway leading to the activation of ERK1 and 2 is required for Mn(2+)-induced PC12 differentiation and neurite outgrowth.
Rat alpha-1-macroglobulin (alpha(1)M) and alpha-2-macroglobulin (alpha(2)M) are murine homologs of human alpha(2)M, and rat alpha(2)M is generally known as an acute-phase protein. Monoamine-activated forms of human alpha(2)M have been shown to inhibit various neuronal functions, but the effect of rat alpha(1)M and acute-phase alpha(2)M on neurons is largely unknown. In this report, rat serotonin-activated alpha(2)M (5HT-alpha(2)M) has been demonstrated to inhibit nerve growth factor (NGF)-promoted neurite extension in pheochromocytoma PC12 cells, and we investigated its possible mechanism of action including its effect on NGF-promoted signal transduction and gene expression in these cells. Especially in the absence of NGF, 5HT-alpha(2)M was found to bind to TrkA (the high-affinity receptor for NGF) much better than normal alpha(2)M (N-alpha(2)M). 5HT-alpha(2)M dose-dependently inhibited NGF-promoted autophosphorylation of TrkA, and decreased the expression of two immediate-early genes (NGFI-A and c-jun) and two delayed-response genes (SCG10 and transin) which are associated with neurite outgrowth in PC12 cells. The unmodified N-alpha(2)M, on the other hand, exhibited very little or no inhibitory effects on neurite extension, Trk phosphorylation, or expression of these genes. The results of this study taken together suggest that monoamine-activated acute-phase rat alpha(2)M appears to inhibit neurite outgrowth in PC12 cells possibly via its direct binding to TrkA and subsequent blocking of TrkA-mediated signal transduction and gene expression.
OBJECTIVE: To determine signalment, clinical signs, concurrent diseases, response to surgical treatment, and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia. DESIGN: Retrospective study. ANIMALS: 56 ferrets with bilateral adrenal tumors or adrenal hyperplasia confirmed histologically following subtotal bilateral adrenalectomy. PROCEDURE: Medical records of all ferrets with bilateral adrenal tumors or hyperplasia examined between 1994 and 1997 were reviewed. Ferrets underwent a subtotal bilateral adrenalectomy or a unilateral adrenalectomy initially, followed by a unilateral subtotal adrenalectomy when tumors or hyperplasia later developed on the contralateral adrenal gland. A long-term follow-up of a minimum of 18 months after final adrenal gland surgery was obtained by examination of medical records and follow-up telephone conversations. RESULTS: Clinical signs of hyperadrenocorticism included bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy (or unilateral adrenalectomy followed by contralateral unilateral subtotal adrenalectomy) was effective with a mortality rate of < 2%. Only 3 (5%) ferrets required glucocorticoid or mineralocorticoid replacement following subtotal bilateral adrenalectomy. Recurrence after bilateral adrenalectomy was 15% with a mean long-term follow-up period of 30 months. CONCLUSIONS AND CLINICAL RELEVANCE: Bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets are indicative of adrenal tumors or adrenal hyperplasia in ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy is effective, with a low rate of complications and postoperative recurrence rate.