The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics

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• 作者：Zsuzsanna Literáti-Nagy (1)
  Kálmán Tory (2)
  Botond Literáti-Nagy (3)
  Attila Kolonics (2)
  Zsolt T?r?k (4)
  Imre Gombos (4)
  Gábor Balogh (4)
  László Vígh Jr. (4) (5)
  Ibolya Horváth (4)
  József Mandl (1)
  Balázs Sümegi (6)
  Philip L. Hooper (7)
  László Vígh (4)
  
• 关键词：HSP ; BGP ; 15 ; Hydroxylamines ; Schizophrenia ; Heat ; shock proteins ; Diabetes ; Metabolic syndrome ; Weight gain ; Insulin resistance ; Mitochondria ; Insulin signaling ; Atypical antipsychotic drugs ; Therapy ; Side effects ; Membranes ; HSP inducers ; HSP72
• 刊名：Cell Stress and Chaperones
• 出版年：2012
• 出版时间：July 2012
• 年：2012
• 卷：17
• 期：4
• 页码：517-521
• 全文大小：228KB
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• 作者单位：Zsuzsanna Literáti-Nagy (1)
  Kálmán Tory (2)
  Botond Literáti-Nagy (3)
  Attila Kolonics (2)
  Zsolt T?r?k (4)
  Imre Gombos (4)
  Gábor Balogh (4)
  László Vígh Jr. (4) (5)
  Ibolya Horváth (4)
  József Mandl (1)
  Balázs Sümegi (6)
  Philip L. Hooper (7)
  László Vígh (4)
  
  1. Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
  2. N-Gene Research and Development Ltd., Budapest, Hungary
  3. Drug Research Center Ltd., Balatonfüred, Hungary
  4. Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726, Szeged, Hungary
  5. Mecsek Pharma Research Ltd., Pécs, Hungary
  6. Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary
  7. Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, CO, 80045, USA
  
• ISSN：1466-1268

文摘

Weight gain and dysfunction of glucose and lipid metabolism are well-known side effects of atypical antipsychotic drugs (AAPD). Here, we address the question whether a heat-shock protein (HSP) co-inducer, insulin sensitizer drug candidate, BGP-15, can prevent AAPD-induced glucose, lipid, and weight changes. We also examined how an AAPD alters HSP expression and whether BGP-15 alters that expression. Four different experiments are reported on the AAPD BGP-15 interventions in a human trial of healthy men, a rodent animal model, and an in vitro adipocyte cell culture system. Olanzapine caused rapid insulin resistance in healthy volunteers and was associated with decreased level of HSP72 in peripheral mononuclear blood cells. Both changes were restored by the administration of BGP-15. In Wistar rats, weight gain and insulin resistance induced by clozapine were abolished by BGP-15. In 3T3L1 adipocytes, clozapine increased intracellular fat accumulation, and BGP-15 inhibited this process. Taken together, our results indicate that BGP-15 inhibits multiple metabolic side effects of atypical antipsychotics, and this effect is likely to be related to its HSP co-inducing ability.