PR:Q53H76 PR phospholipase A1 member A (human) FMA:67514 FMA Lipid bilayer of wall of lysosome GO:0005764 GO lysosome GO:0005739 GO mitochondrion UBERON:0002107 UBERON liver GO:0004620 GO phospholipase activity GO:0048102 GO autophagic cell death HP:0001414 HP Microvesicular hepatic steatosis MP:0014045 MP Mallory bodies MP:0003333 MP liver fibrosis 2 WIKI decreased 7 WIKI functional change 3 WIKI occurrence 1 WIKI increased WikiUser_15 ApacheUser Sprague-Dawley 9606 NCBI Homo sapiens Inhibition, Phospholipase A Molecular AOPWiki 2016-11-29T18:41:27 2016-12-03T16:37:52 Damage, Lipid bilayer Cellular AOPWiki 2016-11-29T18:41:27 2016-12-03T16:37:52 Disturbance, Lysosomal function Cellular CL:0000255 CL eukaryotic cell AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:33 Injury, Mitochondria Cellular CL:0000255 CL eukaryotic cell AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:33 Occurrence, Cytoplasmic vacuolization (hepatocyte) Cellular CL:0000182 CL hepatocyte AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:32 Occurrence, Ballooning degeneration (hepatocyte) Cellular CL:0000182 CL hepatocyte AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:33 Occurrence, Cytoplasmic vacuolization (kupffer cell) Cellular CL:0000091 CL Kupffer cell AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:33 Induction, Microvesicular fat Tissue AOPWiki 2016-11-29T18:41:27 2016-12-03T16:37:52 Formation, Mallory body Cellular AOPWiki 2016-11-29T18:41:27 2016-12-03T16:37:52 Formation, Liver fibrosis Tissue UBERON:0002107 UBERON liver AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:32 Occurrence, Cytoplasmic vacuolization (Bile duct cell) Cellular CL:1000488 CL cholangiocyte AOPWiki 2016-11-29T18:41:27 2017-09-16T10:16:33 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb039310> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb067378> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb07d420> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb0a6ed8> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb0b0ff0> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb0f6f28> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb118dd0> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb14a6f0> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb176bb0> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb1ad070> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb20c6d8> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb268cf8> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb2fbf80> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb320bc8> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb3842b8> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb398858> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ebb63588> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ebbbd740> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ebc3b9b0> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ebcdb230> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ebebb460> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b4311387168> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b43113a77b0> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b4311930cb8> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ebb7e7c0> AOPWiki 2016-11-29T18:41:35 2016-12-03T16:38:01 Inhibition of LPLA2, hepatotoxicity Agnes Aggy <ul> <li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Jung-Hwa Oh,&nbsp;Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea</span></span></li> <li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Seokjoo Yoon,&nbsp;Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea</span></span></li> <li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Hyun Jegal,&nbsp;Department of Human and Environmental Toxicology, University of Science &amp; Technology, Daejeon, 34113, Republic of Korea</span></span></li> </ul> <p>&nbsp;</p> <p>&nbsp;</p> BY-SA Under Development 1.39 1.0 <p style="text-align:justify"><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif"><span style="color:#7f7f7f">Drug-induced phospholipidosis (DIPL) is one of the lipid storage disorders, and some of the cationic amphiphilic drugs (CADs) lead to phospholipids accumulation in the lysosome. Some patients with phospholipidosis have been reported with steatosis, cirrhosis, and fibrosis but the mechanism of their association has not been clarified. CADs can easily pass through membranes due to their amphiphilic character and accumulate in the lysosome of the hepatocyte or alveolar macrophage. These drugs inhibit the activity of lysosomal phospholipase A2 by binding with enzyme or phospholipid, which causes phospholipids to accumulate in lysosome and form a lamellar body. Therefore, CADs led to phospholipidosis along with lysosomal dysfunction. Lysosomes are the predominant digestive organelle and it has the hydrolytic enzymes that degrade peptides, nucleic acids, carbohydrates, and lipids. Lysosomal dysfunction induced to lipid accumulation in the cytosol by inhibiting the lipid metabolism. And lysosomal membrane potential is changed due to accumulating CADs in lysosome and it induced the lysosomal cell death and mitochondrial dysfunction by secondary effects.</span> <span style="color:#7f7f7f">To develop the AOP for phospholipid and hepatotoxicity, we survey the public literature. At present, direct evidence between phospholipidosis and hepatotoxicity is still lacking, but we try to explain using the AOP framework. </span></span></span></p> adjacent Not Specified High adjacent Not Specified High adjacent Not Specified High adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified Low adjacent Not Specified High adjacent Not Specified High High Male Low Unspecific High 1 to < 3 months High Adults High High AOPWiki 2016-11-29T18:41:16 2023-09-25T16:26:51