Levels of Metacaspase1 and Chaperones Related to Protein Maintenance in Alcoholic and Non‐alcoholic Steatohepatitis

Abstract

Metacaspase 1(Mca1), in a recent study, extended the life span of the yeast Saccharomyces cerevisiae. Elevated Mca1 expression counteracted aggregation and accumulation of misfolded proteins and extended life span with the aid of Heat shock protein104 (Hsp104) chaperone(Hill, et al, 2014). Other proteins that play important roles in protein maintenance are Hsp40, Ydj1, SSA1, p97/VCP, and p62. Steatohepatitis is a common liver disorder that presents with a myriad of cellular dysfunction including abnormal protein aggregation. This study aims to measure the expression of Mca1 and related chaperones involved in protein maintenance in alcoholic steatohepatitis(ASH), non-alcoholic steatohepatitis(NASH) and normal control livers. Mca1, Hsp104, Hsp40, Ydj1, SSA1, p97/VCP, and p62 expressions were measured in three to six formalin-fixed paraffin-embedded ASH, NASH and control normal liver specimens by immunofluorescence staining and quantified by immunofluorescence intensity. Mca1, HSP104, Ydj1 and p62 were significantly upregulated compared to control(p<0.05) in ASH specimens. SSA1, Hsp40 and p97/VCP levels did not have significant differences with the control specimens. In NASH, the only significant difference was the increased expression of HSP104 compared to control(p<0.05). Expressions of Mca1, HSP40, p97/VCP, p62, Ydj1, and SSA1 did not show significant differences compared to control. The upregulation of Mca1, HSP104, Ydj1 and p62 in ASH may be elicited as a response to the chronic exposure of the hepatocytes to the toxicity of alcohol. Whereas in NASH, the exposure of hepatocytes to the causative factors does not stimulate an increase in the Mca1 and related chaperones expression.