Acetaldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme responsible for the metabolism of the alcohol metabolite acetaldehyde in the liver. Along with its primary function, ALDH is also involved in other important cellular processes. Several studies have investigated the involvement of ALDH expression in different liver diseases such as viral hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer.
A recent research study published in the journal Gene Expression focuses on the significant role of ALDHs, a group of enzymes, in liver health. This study was led by Smith and colleagues from the Department of Pathology at Tulane University. Its primary objective is to understand and explore the role of ALDHs in catalyzing the irreversible oxidation of various aliphatic and aromatic aldehydes, which are essential for addressing liver diseases, including cancer.
The researchers have used publicly available data from databases like the Human Protein Atlas to analyze the patterns of ALDH expression in different liver zones. They focused on understanding how these enzymes are distributed across various zones in the liver, which is essential in comprehending their role in maintaining liver health and diseases such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA).
One particular enzyme, ALDH2, has been identified as a potential therapeutic target for liver disease. It can prevent acetaldehyde exposure in the reduction of signal transducer and activator of transcription one methylation, which is beneficial in mitigating alcoholic liver disease.
The researchers found that different ALDH enzymes have distinct expression patterns in various liver zones. For example, some enzymes are more prevalent in pericentral zones, while others are dominant in periportal zones. In liver cancers like HCC, specific ALDH enzymes are upregulated, indicating a potential involvement in cancer progression. Conversely, other ALDH enzymes are downregulated, suggesting a loss of protective function.
Similarly, Wang et.al also concluded that ALDH2 expression has been linked with liver cancer risk, pathogenesis, and prognosis, and has emerged as a promising therapeutic target.
In conclusion, the researchers found that the diverse spatial and temporal expression of ALDH enzymes in the liver plays a critical role in maintaining liver health. Alterations in their expression and function are closely associated with the development of liver diseases, including HCC and CCA. A deeper understanding of ALDH genes in the liver, particularly their relation to liver zonation, holds promise for the development of more accurate and personalized approaches for treating liver diseases such as HCC and CCA.
References
- Jin-Smith B, Jn-Simon N, Basha S, Sun C, Wu S, Barkin JM, et al. Acetaldehyde Dehydrogenases in Liver Zonation and Liver Cancer. Gene Expression. 2023 Mar 28;22(1):66–76.
- Wang W, Wang C, Xu H, Gao Y. Aldehyde Dehydrogenase, Liver Disease and Cancer. Int J Biol Sci. 2020 Jan 22;16(6):921–34.