Chronic Ethanol Ingestion Impairs TGF-α-Stimulated Receptor Autophosphorylation

Tuma, Dean J.; Todero, Sandra L.; Barak-Bernhagen, Mary A.; Casey, Carol A.; Sorrell, Michael F.

doi:10.1016/s0741-8329(97)00127-4

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…Specifically, our study demonstrated that while EtOH exposure for 4 and 6 days did not alter erbB1 gene expression or the synthesis of total, non-phosphorylated erbB1 protein, it did cause a marked decrease in the synthesis of the phosphorylated form of the receptor at both 4 days and 6 days. While this is the first report of EtOH altering phosphorylated erbB1 in the prepubertal female hypothalamus, it has previously been reported that chronic EtOH exposure inhibits erbB1 phosphorylation in liver (O’Rourke et al, 1997; Tuma et al, 1998) and stomach (Wang et al, 1997). It is important to note that while we have demonstrated that short-term EtOH exposure did not affect the hypothalamic synthesis of erbB1, as reflected by unaltered gene and total protein expressions, it markedly altered its activity, as reflected by decreased basal phosphorylated erbB1 protein.…”

Section: Discussionmentioning

confidence: 77%

“…However, we cannot rule out the possibility that EtOH may also have a direct effect on the erbB1 autophosphorylation process independent of its effect to suppress TGFα secretion. In this regard, several studies have demonstrated that chronic EtOH exposure influences the phosphorylation of erbB1 by altering the receptor affinity and/or tyrosine kinase activity in rats (Tuma et al, 1998; Wang et al, 1997). …”

Section: Discussionmentioning

confidence: 99%

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Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat

Srivastava

Hiney

Dees

2011

Alcohol

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Glial derived transforming growth factor-α (TGFα) activates the erbB1/erbB2 receptor complex on adjacent glial cells in the medial basal hypothalamus (MBH). This receptor activation stimulates the synthesis and release of prostaglandin-E 2 (PGE 2 ) from the glial cells, which then induces the release of prepubertal luteinizing hormone releasing hormone (LHRH) secretion from nearby nerve terminals; thus, showing the importance of glial-neuronal communications at the time of puberty. Ethanol (EtOH) is known to cause depressed prepubertal LHRH secretion and delayed pubertal development. In this study, we assessed whether short-term EtOH exposure could alter the hypothalamic glial to glial signaling components involved in prepubertal PGE 2 secretion. Immature female rats began receiving control or EtOH diets beginning when 27 days old. The animals were killed by decapitation after 4 and 6 days of treatment and confirmed to be in the late juvenile stage of development. Blood and brain tissues were collected for gene, protein and hormonal assessments. Real-time PCR analysis demonstrated that EtOH did not affect basal levels of erbB1 gene expression in the MBH. Expression of total erbB1 protein was also unaffected; however, the EtOH caused suppressed phosphorylation of erbB1 protein in the MBH at both 4 and 6 days (p<0.01) as revealed by Western blotting. Phosphorylation and totaql protein levels of erbB2 receptor were not affected by EtOH exposure. Because this receptor is critical for PGE 2 synthesis/release, which mediates the secretion of LHRH, we assessed whether in vivo EtOH exposure could affect the release of PGE 2 . EtOH exposure for 6 days suppressed (p<0.01) basal levels of PGE 2 released into the medium. The effects of 4 and 6 day EtOH exposure on gene and protein expressions of TGFα, an upstream component in the activation of erbB1/erbB2, were also studied. The levels of TGFα mRNA were increased markedly at 4 days (p<0.001), but declined to near basal levels by 6 days in the EtOH-treated animals. The EtOH caused increases in TGFα protein expression at both 4 (p<0.001) and 6 (p<0.01) days; hence, suggesting that the EtOH inhibited release of the peptide. We confirmed this inhibition by showing decreased (p<0.01) TGFα released from MBHs incubated in vitro following 6 days of EtOH exposure in vivo. Thus, these results demonstrate that EtOH is capable of interfering with hypothalamic glial to glial signaling processes involved in prepubertal PGE 2 secretion.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat

Srivastava

Hiney

Dees

2011

Alcohol

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“…Chronic ethanol consumption also disrupted complex formation between EGF-R and PLCg (Zhang and Farrel, 1999). Chronic ethanol treatments also inhibited TGF-a induced EGF-R autophosphorylation and binding activity at different TGF-a concentrations (Tuma et al, 1998). Ethanol alone enhances tyrosine kinase activity in cerebral vessels and inhibition of tyrosine kinase activation abolished ethanol induced p42/44 MAPK activation (Yang et al, 2001a,b).…”

Section: Role Of Tyrosine Kinasesmentioning

confidence: 99%

MAP kinase signaling in diverse effects of ethanol

2004

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“…However, we cannot rule out the possibility of a direct action of alcohol on the erbB1 autophosphorylation process that is independent of suppressed TGFα secretion. Several studies supporting this have demonstrated that chronic alcohol exposure disrupts phosphorylation of erbB1 by altering receptor affinity and/or tyrosine kinase activity (Tuma, Todero, Barak-Bernihagen, Casey, & Sorrell, 1998; Wang, Feng, & Wu-Wang, 1997). …”

Section: In Vitro and In Vivo Effects Of Alcohol On Erbb1 Receptor Acmentioning

confidence: 92%

Alcohol alters hypothalamic glial-neuronal communications involved in the neuroendocrine control of puberty: In vivo and in vitro assessments

Dees¹,

Hiney²,

Srivastava³

2015

Alcohol

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The onset of puberty is the result of the increased secretion of hypothalamic luteinizing hormone-releasing hormone (LHRH). The pubertal process can be altered by substances that can affect the prepubertal secretion of this peptide. Alcohol is one such substance known to diminish LHRH secretion and delay the initiation of puberty. The increased secretion of LHRH that normally occurs at the time of puberty is due to a decrease of inhibitory tone that prevails prior to the onset of puberty, as well as an enhanced development of excitatory inputs to the LHRH secretory system. Additionally, it has become increasingly clear that glial-neuronal communications are important for pubertal development because they play an integral role in facilitating the pubertal rise in LHRH secretion. Thus, in recent years attempts have been made to identify specific glial-derived components that contribute to the development of coordinated communication networks between glia and LHRH cell bodies, as well as their nerve terminals. Transforming growth factor-α and transforming growth factor-β1 are two such glial substances that have received attention in this regard. This review summarizes the use of multiple neuroendocrine research techniques employed to assess these glial-neuronal communication pathways involved in regulating prepubertal LHRH secretion and the effects that alcohol can have on their respective functions.

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Chronic Ethanol Ingestion Impairs TGF-α-Stimulated Receptor Autophosphorylation

Cited by 11 publications

References 31 publications

Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat

Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat

MAP kinase signaling in diverse effects of ethanol

Alcohol alters hypothalamic glial-neuronal communications involved in the neuroendocrine control of puberty: In vivo and in vitro assessments

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