Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the anorectic action of AMPH has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study was aimed to examine the molecular mechanisms behind the anorectic effect of AMPH. Results showed that AMPH treatment decreased food intake, which was correlated with changes of NPY mRNA level, but increased c-fos, c-jun and superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or c-jun was involved in the anorectic response of AMPH, infusions of antisense oligonucleotide into the brain were performed at 1 h before daily AMPH treatment in freely moving rats, and the results showed that c-fos or c-jun knockdown could block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c-jun knockdown could partially block SOD mRNA level that might involve in the modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling might involve in the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.
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PMID:Activations of c-fos/c-jun signaling are involved in the modulation of hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression in amphetamine-mediated appetite suppression. 1608 49

Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.
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PMID:Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring. 1661 51

Amphetamine (AMPH), a psychostimulant, is an appetite suppressant and may be regarded as a neurotoxin. It was reported that superoxide dismutase (SOD) and neuropeptide Y (NPY) participated in AMPH-mediated behavior response. However, molecular mechanisms underlying this action are not well known. Using feeding behavior as an indicator, this study investigated if protein kinase C (PKC)-delta signaling was involved. Rats were given daily with AMPH for 4 days. Changes in hypothalamic NPY, PKCdelta and SOD mRNA contents were measured and compared. Results showed that the up-regulations of PKCdelta and SOD mRNA levels following AMPH treatment were concomitant with the down-regulation of NPY mRNA level and the decrease of feeding. To further determine if PKCdelta was involved, intracerebroventricular infusions of PKCdelta antisense oligonucleotide were performed at 1h before daily AMPH treatment in freely moving rats, and results showed that PKCdelta knock-down could block the anorectic response and restore partially both NPY and SOD mRNA levels in AMPH-treated rats. It is suggested that central PKCdelta signaling may play a functional role in the regulation of AMPH-mediated appetite suppression via a modification of hypothalamic NPY gene expression. Moreover, the increase of SOD during AMPH treatment may favor this modification.
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PMID:Amphetamine-evoked changes of oxidative stress and neuropeptide Y gene expression in hypothalamus: regulation by the protein kinase C-delta signaling. 1949 17