Spontaneous activation of pancreas trypsinogen in heat shock protein 70.1 knock-out mice.
OBJECTIVE
Heat shock proteins (Hsp's) protect cellular proteins in response to injury, and the role of Hsp70 in experimental pancreatitis was recently described. To find out the possible role of Hsp70 in pancreatitis, we used Hsp70 knock-out mice (Hsp70.1-/-) and wild-type mice (Hsp70.1+/+).


METHODS
We studied enzymes activities, Hsp70 protein levels, and histologies in cerulein-induced pancreatitis of Hsp70.1-/- and Hsp70.1+/+ mice.


RESULTS
In the basal state, Hsp70 protein levels were higher in Hsp70.1+/+ than in Hsp70.1-/- mice, and trypsin activity was higher in Hsp70.1-/- than in Hsp70.1+/+ mice. The zymogen/lysosome ratio of cathepsin B activity before cerulein injection was higher in Hsp70.1-/- than in Hsp70.1+/+ mice. The expression level of Hsp70 in the pancreas increased in both of Hsp70.1-/- and Hsp70.1+/+ mice after hyperthermia because of the Hsp70.3 gene left intact in Hsp70.1-/- mice. After cerulein hyperstimulation, trypsin activity increased 2-fold in Hsp70.1+/+ mice, but cerulein did not further increase basally elevated trypsin activity in Hsp70.1-/- mice. Hyperthermia pretreatment not only blocked cerulein-induced trypsinogen activation, pancreatic edema, and vacuolization in Hsp70.1+/+ mice, but also decreased basally elevated trypsin activity in Hsp70.1-/- mice.


CONCLUSIONS
Hsp70 can be responsible for inhibition of cerulein-induced pancreatitis and prevention of spontaneous trypsinogen activation in mice by inhibiting the colocalization of zymogen and lysosomal enzymes.
Hwang
Jin-Hyeok
JH
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
Ryu
Ji Kon
JK
Yoon
Yong Bum
YB
Lee
Kwang Hyuck
KH
Park
Young-Soo
YS
Kim
Jin-Wook
JW
Kim
Nayoung
N
Lee
Dong Ho
DH
Jeong
Ji Bong
JB
Seo
Jeong-Sun
JS
Kim
Yong-Tae
YT
D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D004789:Enzyme Activation; D005334:Fever / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000201:enzymology*; D010195:Pancreatitis / Q000473:pathology / Q000517:prevention & control; D014362:Trypsinogen / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; C081884:heat-shock protein 70.1; D014362:Trypsinogen; D002401:Cathepsin B