ANG - Angiogenin | Elisa - Clia - Antibody - Protein

Background:

Angiogenin (ANG) is a protein that plays a significant role in angiogenesis. It is a member of the ribonuclease superfamily, but unlike other members that primarily function in RNA degradation, angiogenin has distinct functions related to blood vessel formation and tissue repair. The primary role of angiogenin is to promote the growth of new blood vessels from existing ones. This is crucial in processes like wound healing, embryonic development, and tissue regeneration. Angiogenin has ribonuclease activity, meaning it can cleave RNA molecules. However, its angiogenic activity is independent of this enzymatic function. Angiogenin acts on endothelial cells, which line the inside of blood vessels. It stimulates these cells to proliferate, migrate, and form new blood vessels. It also promotes cell survival and protects cells from apoptosis (programmed cell death), which is important for the stability of newly formed blood vessels.

Protein Structure:

• Primary Structure: Angiogenin consists of 123 amino acids.
• Tertiary Structure: The protein has a compact, globular structure characterized by a high content of beta-sheets and disulfide bonds, which stabilize its conformation.
• Active Site: Despite its similarity to ribonucleases, the ribonucleolytic activity of ANG is much lower. Its active site includes histidine residues that are essential for its enzymatic function, though these are not the primary contributors to its angiogenic activity.

Classification and Subtypes:

• Family: Angiogenin is part of the ribonuclease A superfamily.
• Isoforms: There are no widely recognized subtypes or isoforms of angiogenin, but its expression can be regulated at the transcriptional and post-transcriptional levels in various tissues.

Function and Biological Significance:

• Angiogenesis: Angiogenin promotes the proliferation and migration of endothelial cells, which line the interior surface of blood vessels. It also helps in the formation of tubular structures that eventually develop into new blood vessels.
• Ribonuclease Activity: Although ANG possesses ribonuclease activity, its angiogenic function is largely independent of this enzymatic activity. The ribonuclease function is thought to play a role in other cellular processes, such as rRNA processing and stress response.
• Neuroprotection: Angiogenin has been implicated in neuroprotection and is found to be upregulated in response to neuronal injury.
• Cell Survival: ANG is involved in cell survival pathways and has been shown to protect cells under stress conditions.

Interactions:

• Receptors: Angiogenin interacts with cell surface receptors, such as the 67-kDa laminin receptor and actin on the cell surface, to mediate its angiogenic effects.
• Nuclear Translocation: Upon binding to its receptors, angiogenin is internalized and translocated to the nucleus, where it can influence the expression of genes involved in cell growth and survival.

Clinical Issues:

• Cancer: Angiogenin is overexpressed in various cancers, including pancreatic, colorectal, and prostate cancers, where it contributes to tumor growth and metastasis by promoting angiogenesis.
• Amyotrophic Lateral Sclerosis (ALS): Mutations in the ANG gene have been associated with familial and sporadic forms of ALS, suggesting a neuroprotective role for angiogenin.
• Therapeutic Potential: Angiogenin is a target for anti-angiogenic therapies in cancer treatment. In contrast, its angiogenic and neuroprotective properties are being explored for therapeutic use in ischemic diseases and neurodegenerative disorders.

Summary:

Angiogenin is a multifunctional protein primarily known for its role in promoting angiogenesis. Structurally related to ribonucleases, it exhibits unique properties that facilitate endothelial cell proliferation and new blood vessel formation. Beyond its angiogenic role, angiogenin is involved in neuroprotection, cell survival, and is implicated in various pathological conditions, including cancer and neurodegenerative diseases. Its dual role in promoting cell growth and protecting neurons makes it a significant focus of research for developing both anti-cancer therapies and treatments for neurodegenerative diseases. Understanding the mechanisms of angiogenin's action and its interactions with cellular components is crucial for harnessing its therapeutic potential.