Actin overexpression parallels severity of pancreatic injury.
Among the three major cytofilament proteins, keratin (K8/K18/K19) expression increases nearly threefold upon pancreas or liver injury, while actin and tubulin expressions are considered relatively stable. K8/K18 serves essential hepatocyte cytoprotective functions yet appears dispensable in K8-null mouse pancreata, which led us to hypothesize that actin or tubulin expressions may increase after pancreatic injury. Balb/c and FVB/n mice manifested different susceptibility to injury in two pancreatitis models, with significant induction of actin protein (threefold) and RNA after moderate or severe but not mild injury. Alterations in tubulin expression were less prominent. Basally, K8-null and wild-type pancreata expressed similar actin and tubulin levels, while the injury-induced actin protein but not RNA was more pronounced in K8-null mice. K7/K18/K19/K20 were also induced in K8-null mice after injury. Ex vivo, caerulein-triggered pancreatitis caused protein degradation (actin approximately or = tubulin > keratins) and mRNA up-regulation that was blocked by actinomycin-D (act-D) (actin approximately or = tubulin approximately or = keratin) or by NF-kappaB inhibition (keratins > actin approximately or = tubulin). Hence, actin is not as static as previously held and is overexpressed after moderate to severe pancreatic injury while keratins are induced after minimal injury. Keratin and actin induction may serve protective roles in pancreatic injury.
Zhong
Bihui
B
Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Omary
M Bishr
MB
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002108:Ceruletide / Q000009:adverse effects; D003599:Cytoskeleton; D003609:Dactinomycin / Q000494:pharmacology; D004198:Disease Susceptibility / Q000473:pathology; D005260:Female; D015151:Immunoblotting; D053533:Keratin-8; D007633:Keratins / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010179:Pancreas / Q000293:injuries* / Q000378:metabolism*; D010182:Pancreatic Diseases / Q000139:chemically induced*; D010195:Pancreatitis / Q000139:chemically induced*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
D000199:Actins; D053533:Keratin-8; C486595:Krt8 protein, mouse; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014404:Tubulin; D003609:Dactinomycin; D007633:Keratins; D002108:Ceruletide