TY - JOUR
T1 - Altered expression and phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in postmortem brain of suicide victims with or without depression
AU - Pandey, Ghanshyam N.
AU - Dwivedi, Yogesh
AU - Ren, Xinguo
AU - Rizavi, Hooriyah S.
AU - Roberts, Rosalinda C.
AU - Conley, Robert R.
AU - Tamminga, Carol
N1 - Funding Information:
This work was supported by a grant from the National Institute of Mental Health (RO1MH 48153-04) to G.N. Pandey. Brain collection was supported in part by a grant (MH 40279) to W. Carpenter. We acknowledge with thanks the cooperation of Dr. John Smialek, Chief Medical Examiner, and Dr. Dennis Chute, Assistant Medical Examiner, Ms. Terri U'Prichard for help in performing psychological autopsies, Ms. Barbara Brown and Ms. Miljana Petkovic for technical assistance.
PY - 2003
Y1 - 2003
N2 - Myristoylated alanine-rich C kinase substrate (MARCKS), an acidic, heat-stable protein, is involved in important physiological functions such as neurotransmitter release and re-uptake. It is also a substrate for phosphorylation by protein kinase C (PKC) and has been shown to play a role in the pathophysiology of mood disorders. In this study, protein and mRNA expression of MARCKS as well as phosphorylation of MARCKS were determined in the prefrontal cortex (PFC) and hippocampus of postmortem brain obtained from suicide victims, with or without depression, and normal control subjects. There were no significant differences in mRNA and protein levels of MARCKS between suicide subjects and controls. However, protein levels of MARCKS were significantly increased in the membrane but not in cytosol fraction of PFC and hippocampus obtained from depressed suicide subjects as compared to normal controls. When PKC-mediated MARCKS phosphorylation was determined, it was observed that MARCKS phosphorylation was significantly decreased in the membrane fraction of PFC and hippocampus obtained from total suicide subjects as well as depressed and non-depressed suicide subjects compared with control population. Although the mechanism of such alterations in MARCKS in depressed and non-depressed suicide subjects is not clear, results of the present study indicate that an increase in membrane MARCKS is associated with depressed suicide victims and a decrease in MARCKS phosphorylation may be a common feature of suicide victims independent of diagnosis.
AB - Myristoylated alanine-rich C kinase substrate (MARCKS), an acidic, heat-stable protein, is involved in important physiological functions such as neurotransmitter release and re-uptake. It is also a substrate for phosphorylation by protein kinase C (PKC) and has been shown to play a role in the pathophysiology of mood disorders. In this study, protein and mRNA expression of MARCKS as well as phosphorylation of MARCKS were determined in the prefrontal cortex (PFC) and hippocampus of postmortem brain obtained from suicide victims, with or without depression, and normal control subjects. There were no significant differences in mRNA and protein levels of MARCKS between suicide subjects and controls. However, protein levels of MARCKS were significantly increased in the membrane but not in cytosol fraction of PFC and hippocampus obtained from depressed suicide subjects as compared to normal controls. When PKC-mediated MARCKS phosphorylation was determined, it was observed that MARCKS phosphorylation was significantly decreased in the membrane fraction of PFC and hippocampus obtained from total suicide subjects as well as depressed and non-depressed suicide subjects compared with control population. Although the mechanism of such alterations in MARCKS in depressed and non-depressed suicide subjects is not clear, results of the present study indicate that an increase in membrane MARCKS is associated with depressed suicide victims and a decrease in MARCKS phosphorylation may be a common feature of suicide victims independent of diagnosis.
KW - Depression
KW - MARCKS
KW - MARCKS phosphorylation
KW - PKC
KW - Suicide
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U2 - 10.1016/S0022-3956(03)00047-5
DO - 10.1016/S0022-3956(03)00047-5
M3 - Article
C2 - 12849934
AN - SCOPUS:0038721947
SN - 0022-3956
VL - 37
SP - 421
EP - 432
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
IS - 5
ER -