PMID- 10319918
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20161124
IS  - 0952-3278 (Print)
IS  - 0952-3278 (Linking)
VI  - 60
IP  - 1
DP  - 1999 Jan
TI  - Effect of cis-unsaturated fatty acids on the activity of protein kinases and 
      protein phosphorylation in macrophage tumor (AK-5) cells in vitro.
PG  - 55-63
AB  - Cis-unsaturated fatty acids (c-UFAs) have been shown to be capable of decreasing 
      the survival of macrophage tumor (AK-5) cells in vitro. This cytotoxic action of 
      c-UFAs was found to be associated with an increase in free radical generation and 
      lipid peroxidation process and a simultaneous decrease in cellular anti-oxidants 
      such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione 
      reductase, glutathione and vitamin E. In the present study, it was observed that 
      c-UFAs such as gamma linolenic acid (GLA), arachidonic acid (AA), 
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can activate 
      phospholipase C (PLC) and enhance diacylglycerol formation; all the fatty acids 
      except alpha linolenic acid (ALA) increased the binding of phorbol dibutyrate 
      acetate (PDBu) suggesting translocation of protein kinase C (PKC) and at the same 
      time these fatty acids (especially GLA, AA, EPA and DHA) also enhanced PKC 
      activity. AA, EPA and DHA decreased the activity of protein kinase A (PKA) both 
      in the cytosol and particulate fractions whereas ALA and GLA enhanced the PKA 
      activity in the particulate fractions; all the fatty acids except ALA reduced 
      cyclic AMP levels and an enhanced phosphorylation of about 13 proteins of the 
      nuclear fraction and about eight proteins of the plasma membrane fraction was 
      noted in c-UFA treated AK-5 cells in vitro. These results suggest that c-UFAs can 
      alter the activities of second messenger systems such as diacylglycerol and 
      protein kinases and can phosphorylate both plasma membrane and nuclear proteins 
      which are likely to be components of NADPH oxidase. Based on these results, it is 
      suggested that fatty acids may mediate their cytotoxic action in part by 
      modulating the expression of PKC. Activated PKC may then intensify the 
      pro-oxidant state by augmenting NADPH oxidase, so inducing superoxide anion 
      generation which may ultimately lead to cytolysis.
FAU - Padma, M
AU  - Padma M
AD  - Division of Internal Medicine, Clinical Immunology and Biochemistry, L.V. Prasad 
      Eye Institute, Banjara Hills, Hyderabad, India.
FAU - Das, U N
AU  - Das UN
LA  - eng
PT  - Journal Article
PL  - Scotland
TA  - Prostaglandins Leukot Essent Fatty Acids
JT  - Prostaglandins, leukotrienes, and essential fatty acids
JID - 8802730
RN  - 0 (Diglycerides)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 11062-77-4 (Superoxides)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.1.32 (Phospholipases A)
SB  - IM
MH  - Animals
MH  - Diglycerides/analysis
MH  - Dose-Response Relationship, Drug
MH  - Escherichia coli/metabolism
MH  - Fatty Acids, Unsaturated/*pharmacology
MH  - Macrophages/*drug effects
MH  - Phorbol 12,13-Dibutyrate/metabolism
MH  - Phospholipases A/analysis
MH  - Phosphorylation/drug effects
MH  - Protein Binding/drug effects
MH  - Protein Kinase C/analysis
MH  - Protein Kinases/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Superoxides
MH  - Tumor Cells, Cultured
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - S0952-3278(98)90008-4 [pii]
AID - 10.1054/plef.1998.0008 [doi]
PST - ppublish
SO  - Prostaglandins Leukot Essent Fatty Acids. 1999 Jan;60(1):55-63. doi: 
      10.1054/plef.1998.0008.