Ethanol consumption decreases the synthesis of the mannose 6-phosphate/insulin-like growth factor II receptor but...

Area of Science:

• Molecular Biology
• Hepatology
• Biochemistry

Background:

• The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-IIR) is crucial for lysosomal enzyme transport.
• Chronic ethanol consumption is known to decrease M6P/IGF-IIR protein levels in rat hepatocytes.

Purpose of the Study:

• To investigate whether reduced M6P/IGF-IIR protein content due to ethanol is linked to changes in mRNA levels or protein synthesis rates.
• To determine the impact of ethanol on M6P/IGF-IIR mRNA stability and receptor synthesis in rat hepatocytes.

Main Methods:

• Rats were fed liquid diets with or without ethanol for 7-8 weeks.
• Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify M6P/IGF-IIR mRNA levels in hepatocytes and liver tissue.
• Hepatocytes were radiolabeled to measure total protein and M6P/IGF-IIR protein synthesis rates.

Main Results:

• Ethanol consumption did not alter the steady-state levels of M6P/IGF-IIR mRNA in hepatocytes or whole livers.
• Hepatocytes from ethanol-fed rats exhibited a 70% reduction in receptor synthesis and a 53% lower relative rate of receptor synthesis.
• Total M6P/IGF-IIR protein synthesis rate declined by 79% in ethanol-fed rats compared to controls.

Conclusions:

• The reduction in M6P/IGF-IIR protein content caused by ethanol is partly due to decreased receptor protein synthesis.
• Ethanol consumption does not affect M6P/IGF-IIR mRNA levels, suggesting post-transcriptional regulation.
• Defective M6P/IGF-IIR mRNA translation may explain the ethanol-induced decline in receptor protein synthesis.