Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxia (SCA) 6 is caused by small expansion of a polyglutamine sequence, encoded by CAG trinucleotide repeats, at the C-terminal end of the human CaV2.1 (P/Q-type) Ca2+ channel alpha12.1 subunit and it manifests itself as slowly progressive cerebellar ataxia. To elucidate the pathogenic mechanisms underlying SCA6, we introduced CAG repeats of various lengths into the Ca2+ channel alpha12.1 subunit cDNA and expressed them in baby hamster kidney cells stably expressing the auxiliary subunits (alpha2delta and beta4). The occurrence of cell death differed between cells transfected with the normal and mutant Ca2+ channels under the condition of serum starvation plus potassium-induced depolarization, and Cdk inhibition elucidated the differences more clearly. The CaV2.1 (P/Q-type) Ca2+ channel-specific blocker omega-agatoxin IVA abolished the cell-death-preventing effect of the normal Ca2+ channel. Together with our previous finding that the polyglutamine expansion in SCA6 interferes with the Ca2+ channel to reduce Ca2+ influx, these results indicate that impaired function of the mutant Ca2+ channels rendered them unable to prevent cell death.
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PMID:Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of CaV2.1 Ca2+ channel--loss-of-function cellular model of SCA6. 1547 58

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias. The gene mutated in this disease, ATM (A-T, mutated), encodes a 370-kDa Ser/Thr protein kinase. ATM not only mediates cellular response to DNA damage but also acts as an activator of Akt in response to insulin. However, despite intensive studies, the mechanism underlying the neuronal degeneration symptoms of human A-T is still poorly understood. We found that the topoisomerase inhibitors etoposide and camptothecin readily induced apoptosis in undifferentiated proliferating SH-SY5Y cells but could not induce apoptosis in neuronally differentiated SH-SY5Y cells. In addition, etoposide induced p53 phosphorylation and H2AX foci formation in proliferating SH-SY5Y cells but failed to do so in differentiated SH-SY5Y cells. Moreover, while inhibition of ATM in undifferentiated SH-SY5Y cells partially protected them from etoposide-induced apoptosis, the same treatment had no effect on cell viability in differentiated SH-SY5Y cells. These results suggest that DNA damage or defective response to DNA damage is not the cause of neuronal cell death in human A-T. In contrast, we discovered that Akt phosphorylation was inhibited when ATM activity was suppressed in differentiated SH-SY5Y cells. Furthermore, inhibition of ATM induced apoptosis following serum starvation in neuronally differentiated SH-SY5Y cells but could not trigger apoptosis under the same conditions in undifferentiated proliferating SH-SY5Y cells. These results demonstrate that ATM mediates the Akt signaling and promotes cell survival in neuron-like human SH-SY5Y cells, suggesting that impaired activation of Akt is the reason for neuronal degeneration in human A-T.
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PMID:Functional switching of ATM: sensor of DNA damage in proliferating cells and mediator of Akt survival signal in post-mitotic human neuron-like cells. 2273 65

Gayet Wernicke encephalopathy (EGW) is a neurological emergency secondary to thiamine deficiency (vitamin B1). This is more often secondary to chronic alcoholism. The purpose of this study is to remind clinicians of some clinical signs different from ethylism, suggesting EGW as well as to report four cases characterized by different types of anomalies shown by MRI. The average age of patients was 40 years (2 females 2 males). The neurological picture was characterized by disorders of vigilance in all patients, oculomotor disorders in 2 cases, and cerebellar ataxia in one patient. Chronic vomiting was reported in two cases, prolonged fasting in the first case and alcoholism in the second case. MRI of the brain showed anomalies suggesting EGW in all patients with contrast enhancement in one case. Thiamin deficiency was confirmed in two patients. In our context EGW seems to be more frequent in pathological circumstances other than chronic alcoholism (chronic vomiting, severe malnutrition, severe starvation, and chemotherapy...). The clinical signs can suggest other pathologies such as cerebral venous thrombosis, stroke, or other metabolic disorders but MRI excluded them and allowed the diagnosis of EGW. MRI of the brain has an essential role in the diagnosis of EGW. Absence or delay in treatment may influence the prognosis.
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PMID:[Gayet-Wernicke encephalopathy: clinical features and radiological anomalies]. 3301 55