ALDH1A1: A Protein Of Many Hats

It’s Saturday night and you’re getting a few drinks with friends. Someone suggests shots, and afterward you notice that one of your friends is bright red. “Did you get sunburnt today?” you ask.

“It’s Asian glow!” she says, “I’m Taiwanese, so I don’t have the gene that breaks down alcohol.”

"Asian glow," or "Asian flush," impacts about 40% of people with East Asian ancestry and can result from variations in the gene that codes for alcohol dehydrogenase (ADH)1. Dehydrogenases are enzymes that facilitate the metabolism of alcohols, aldehydes, and ketones. The resulting build-up of aldehydes leads to the redness seen when alcohol is consumed by someone with a faulty copy of the ADH that metabolizes, or breaks down, ethanol.

There are many kinds of ADH, as many as there are types of alcohols, and they can have many functions. ALDH1A1, or aldehyde dehydrogenase 1 family member A1, is also called retinaldehyde dehydrogenase 1 (RALDH1) and metabolizes retinoic acid, broken down from Vitamin A2. In addition to processing Vitamin A, ALDH1A1 is involved in obesity and diabetes, metabolizes some common anticancer drugs, and serves as a biomarker for many cancers3.

Acting through metabolism, ALDH1A1 is complicit in obesity and diabetes etiology. ALDH1A1 protein levels are closely tied to formation of white adipose tissue. There appears to be a sex difference in how ALDH1A1 regulates these diseases. Female mice with deficient copies of ALDH1A1 were resistant to high fat diet-induced obesity and diabetes4. Another study showed elevated levels of ALDH1A1 protein in obese women, indicating that estrogen may be impacting the regulatory role of ALDH1A15.

Regulating metabolism is only one action of ALDH1A1. ALDH1A1 protein is also the primary biomarker, or biological indicator, for stem cells and cancer cells3. How ALDH1A1 regulates cancer cells is unknown, but one hypothesis is that its detoxifying properties protect the cancer from anticancer drugs and reactive oxygen species, free radicals that result from oxidative stress3. Surprisingly, high ALDH1A1 protein levels do not always mean poor clinical outcomes. For example, high ALDH1A1 protein levels in liver and ovarian cancer are favorable, but high levels in esophageal, stomach, and breast cancer are poor. Lung and pancreatic cancer prognosis have mixed association with ALDH1A1 protein levels3.

ALDH1A1 protein is found in the cytoplasm of many cell types, so its levels can be tested by performing a biopsy of the tumor and using immunohistochemistry. An antibody to ALDH1A1 can indicate the level of protein in the cells, giving the clinician a better idea of the patient prognosis according to the cancer type. High ALDH1A1 protein levels might mean the cancer cells are growing and may be resistant to chemotherapy drugs3. This same assay can be performed for metabolism and obesity research as well.

Whether your experiments focus on alcohol metabolism, diabetes, obesity, or cancer, you can use ALDH1A1 antibodies to reveal the location and amount of ALDH1A1 in relevant cells. This information may unlock your next important discovery.

Bethyl offers a recombinant monoclonal ALDH1A1 antibody to meet your research needs.

Detection of human ALDH1A1 in FFPE breast carcinoma by IHC.
Detection of human ALDH1A1 in FFPE breast carcinoma by IHC. Antibody: Rabbit anti-ALDH1A1 recombinant monoclonal [BLR089G] (A700-089). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P). Substrate: DAB.
Detection of human ALDH1A1 in FFPE NCI-H2286 cells by ICC.
Detection of human ALDH1A1 in FFPE NCI-H2286 cells by ICC. Antibody: Rabbit anti-ALDH1A1 recombinant monoclonal [BLR089G] (A700-089). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P). Substrate: DAB.
Detection of human ALDH1A1 in FFPE lung carcinoma by IHC.
Detection of human ALDH1A1 in FFPE lung carcinoma by IHC. Detection of human ALDH1A1 in FFPE lung carcinoma by IHC. Antibody: Rabbit anti-ALDH1A1 recombinant monoclonal [BLR089G] (A700-089). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P). Substrate: DAB.

References

1. Lee H, Kim SS, You KS, Park W, Yang JH, Kim M and Hayman LL. 2014. Asian flushing: genetic and sociocultural factors of alcoholism among East asians. Gastroenterol Nurs. Sep-Oct 37(5): 327-336.

2. Blaner WS. 2019. Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders. Pharmacol Ther. May 197: 153-178.

3. Tomita H, Tanaka K, Tanaka T and Hara A. 2016. Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget. Mar 8 7(10): 11018-11032.

4. Ziouzenkova O, Orasanu G, Sharlach M, Akiyama TE, Berger JP, Viereck J, Hamilton JA, Tang G, Dolnikowski GG, Vogel S, Duester G and Plutzky J. 2007. Retinaldehyde represses adipogenesis and diet-induced obesity. Nat Med. Jun 13(6): 695-702.

5. Yasmeen R, Reichert B, Deiuliis J, Yang F, Lynch A, Meyers J, Sharlach M, Shin S, Volz KS, Green KB, Lee K, Alder H, Duester G, Zechner R, Rajagopalan S and Ziouzenkova O. 2013. Autocrine function of aldehyde dehydrogenase 1 as a determinant of diet- and sex-specific differences in visceral adiposity. Diabetes. Jan 62(1): 124-136.