Science Links Japan | Inhibitory Effect of the .ALPHA.1-Antitrypsin Pittsburgh Type-Mutant(.ALPHA.1-PIM/R) on Proinsulin Processing in the Regulated Secretory Pathway of the Pancreatic .BETA.-Cell Line MIN6.

Inhibitory Effect of the .ALPHA.1-Antitrypsin Pittsburgh Type-Mutant(.ALPHA.1-PIM/R) on Proinsulin Processing in the Regulated Secretory Pathway of the Pancreatic .BETA.-Cell Line MIN6.

Accession number;03A0147504

Title;Inhibitory Effect of the .ALPHA.1-Antitrypsin Pittsburgh Type-Mutant(.ALPHA.1-PIM/R) on Proinsulin Processing in the Regulated Secretory Pathway of the Pancreatic .BETA.-Cell Line MIN6.

Author; OHKUBO K (Fukuoka Univ. School Of Medicine, Fukuoka, Jpn) NAITO Y (Fukuoka Univ. School Of Medicine, Fukuoka, Jpn) FUJIWARA T (Fukuoka Univ. School Of Medicine, Fukuoka, Jpn) MIYAZAKI J (Osaka Univ. Graduate School Of Medicine, Suita, Jpn) IKEHARA Y (Fukuoka Univ. School Of Medicine, Fukuoka, Jpn) ONO J (Fukuoka Univ. School Of Medicine, Fukuoka, Jpn)

Journal Title;Endocr J

Journal Code:F0625A

ISSN:0918-8959

VOL.50;NO.1;PAGE.9-20(2003)

Figure&Table&Reference;FIG.6, TBL.2, REF.39

Pub. Country;Japan

Language;English

Abstract;To elucidate its effect on proinsulin processing, we introduced the expression of a Pittsburgh type-mutant, .ALPHA.1-protease inhibitor M/R(.ALPHA.1-PIM/R) and its chimera protein with growth hormone(GH)(GH.ALPHA.1-PIM/R) into MIN6 cells. In metabolic labeling and chasing experiments with [3H]-Leu and [35S]-Met, proinsulin appeared in the medium during stimulatory secretion only from MIN6 clones expressing GH.ALPHA.1-PIM/R and, surprisingly, .ALPHA.1-PIM/R, but not from the clones of either the control or .ALPHA.1-PI. The major part of .ALPHA.1-PIM/R was secreted through the constitutive pathway and about 10% of total secreted .ALPHA.1-PIM/R in the chase periods entered the regulated pathway. On the other hand, GH.ALPHA.1-PIM/R was mainly transported to the secretory granules and about 80% of the total secreted GH.ALPHA.1-PIM/R in the chase periods was secreted during stimulatory secretion. In the first 3h chase periods without stimulation, only .ALPHA.1-PIM/R and no GH.ALPHA.1-PIM/R appeared in the medium, thus suggesting that .ALPHA.1-PIM/R might be transported through a constitutive-like pathway for those periods. The .ALPHA.1-PI, which had no inhibitory effect on proinsulin processing, showed similar secretion pathways to those of .ALPHA.1-PIM/R. This implies that some part of .ALPHA.1-PIM/R and .ALPHA.1-PI entered the regulated pathway, not due to any specific interaction between the processing endoproteases and serine protease inhibitors, but due to some type of passive transport in a nonselective manner. The inhibitory effect of .ALPHA.1-PIM/R in the regulated secretory pathway was slightly but clearly evident when it was expressed in MIN6 .BETA.-cells. (author abst.)

Related Articles;