Palmitate induced lipoapoptosis of exocrine pancreas AR42J cells.
Chronic surplus of dietary consumption, typical to obesity, results in overflow of fat to non-adipose tissues. Intracellular accumulation of fat in non-adipose tissues is associated with cellular dysfunction and cell death and ultimately contributes to the pathogenesis of chronic diseases. The influence of fat overflow on the exocrine pancreas is not known. The purpose of this research was to study the lipotoxic and lipoapoptotic effect of prolonged (72 h) long chain saturated palmitic fatty acid (0.1 mM) on the survival of exocrine pancreas AR42J cells. We demonstrate that chronic exposure of AR42J cells to palmitic acid results in significant increase in triglycerides accumulation (up to 25% of cells area), compared to untreated cultures. Lipid accumulation prompted a typical apoptotic process, demonstrated by both DNA fragmentation and condensed chromatin appearance (DAPI staining). Quantitative real-time PCR studies demonstrated that prolonged palmitic acid supplementation induced down-regulation of the anti-apoptotic Bcl2 mRNA levels (22%) and up-regulation of the pro-apoptotic Bax mRNA levels (300%), leading to disruption of the pro/anti apoptotic balance (Bax/Bcl2=3). No major change was detected in iNOS mRNA expression. In conclusion, prolonged exposure to saturated palmitic acid induces lipoapoptosis in exocrine pancreatic AR42J cells, through disturbance of the Bax/Bcl-2 balance.
Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.
Z
Z
Landau
E
E
Forti
M
M
Alcaly
R Z
RZ
Birk
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001391:Azo Compounds / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D004396:Coloring Agents / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology*; D005456:Fluorescent Dyes; D007211:Indoles; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D046790:Pancreas, Exocrine / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000378:metabolism
D001391:Azo Compounds; D004396:Coloring Agents; D018076:DNA, Complementary; D005230:Fatty Acids, Nonesterified; D005456:Fluorescent Dyes; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D019308:Palmitic Acid; C007293:DAPI; D052247:Nitric Oxide Synthase Type II; C011049:oil red O